CASE REPORT: A woman in her Early 40’s who has Diminished Ovarian Reserve Requiring IVF with Embryo Banking and PGS.

Hi Dr Sher,
I’m 42 years of age. Until very recently, I knew nothing about IVF, and I now find myself in a scramble to optimize my chances with it.

Despite a lifelong dream of having a healthy baby and happy family, it has taken me this long to find a great man/dad I can believe in for my unborn kids, so prior, I always used protection and never tried to get pregnant. Since my mom got pregnant naturally at 40, I grew up thinking that was normal-or at least normal for my family. And, I thought if I did have a problem, IVF was supposed to be for older women……..even into their late forties. I also never got to try naturally with my partner because as soon as we committed and were ready to start, he was diagnosed w cancer. Within a couple weeks we had his sperm frozen and we set off to focus on his 6 months of chemo (completed), followed by a stem cell transplant (next month). We fit my first IVF appointment into this window.

Although I asked for guidance when we had the sperm frozen, no one told me to rush based on my age. I spent the time trying to take care of him and research his cancer so we could make the best choices for his treatment. So I’m only finding out all the ins and outs of IVF now, and my initial appointment was a total shock! What I thought would be informational and the beginning of a process that was made for me has suddenly turned into a desperate race for a finish line that I may have already missed.

I just finished my initial testing. I don’t think I have the official labeling for all markers like the rest of the people here, but I will try. My IVF doctor described my follicles as being good/adequate. The number I think was 3-4 in each ovary which met his minimum of what he likes to see. My AMH was .87. My FSH was described over the phone as “good” but I was told my estrogen was high at 107, therefore my FSH was unreliable. I was then told I’d be doing the Micro Flare Lupron protocol. My appointment to get all the details is tomorrow.

To find out more, I got online and that is where I found you and read these articles about NOT doing the micro flare specifically for people of advanced reproductive age (even though it’s described elsewhere as something to do exactly for that).

As it is now, I’m just at the cut-off for fitting in a cycle before the winter break. If I have to wait to start until January-February, I’ll have lost another 4-5 months in this race.

In your opinion, is my doctor wrong? If so, how should I challenge him and still have a good relationship and have us both feel confident? If he doesn’t agree to a new plan such as what you describe, should I look for someone else, even at the expense of waiting until next year? Is there a way to approach another doctor with all my results and have this discussion to see if they can start me in this upcoming cycle on the kind of protocol you suggest?

The plan is to do an all freeze cycle, then PGS, then transfer normal embryos about 6 months, after my partner has recovered from his transplant.

Thank you so much!

 

________________________________________________________________________

MY RESPONSE:

Hi R,

Your story is so very, very heart-rending and I really would like to be of assistance to you without being intrusive. It simply would not be right for me to inject myself into your treatment plan as you are being treated by another physician. However, I would like you to know that in spite of your advanced “biological clock” (age (42y) and diminished ovarian reserve (DOR) (AMH=0.87ng/ml) there is in my opinion, still a modest window of opportunity for you to have a baby using your own eggs. However, to be successful, you cannot afford to spin your wheels. You need to be proactive and strategic and engage ASAP.

I cannot provide you with specific directives and would not be so presumptuous as to tell you how to approach your treating physician, however I am willing to provide you with an insight into how I deal with such cases and as to why I take such an approach. This having been said, you should know that what follows represents my personal opinion which is not shared by all in the field.

So here goes: You see, the older a woman becomes, the more likely it is that her eggs will be chromosomally/genetically “incompetent” (not have the potential upon being fertilized and transferred, to result in a viable pregnancy). That is why, the likelihood of failure to conceive, miscarrying and of giving birth to a chromosomally defective child (e.g. with Down syndrome) increases with the woman’s advancing age. In addition, as women age beyond 35Y there is commonly a progressive diminution in the number of eggs left in the ovaries, i.e. diminished ovarian reserve (DOR). So it is that older women as well as those who (regardless of age) have DOR have a reduced potential for IVF success. Much of this is due to the fact that such women tend to have increased production of LH biological activity which can result in excessive LH-induced ovarian male hormone (predominantly testosterone) production which in turn can have a deleterious effect on egg/embryo “competency”.

While it is presently not possible by any means, to reverse the age-related effect on the woman’s “biological clock,” certain ovarian stimulation regimes, by promoting excessive LH production (e.g. short agonist/Lupron- “flare” protocols, clomiphene and Letrozole), can 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 older women and those 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.

I hope this information helps you and I wish you good fortune in your upcoming IVF journey.

Sincerely,

Geoff Sher

8 Comments

Cinthia

Hi doctor Sher, so accordingly whith what I read from your blog the best approach for old woman is starting always with oral contraceptive pills and overlapp with Lupron 2 days? I am so afraid the pill could suppress in advance my ovaries! Isn’t it?

reply
Dr. Geoffrey Sher

One often hears the expressed opinion that the BCP suppresses response to ovarian stimulation. This is not the case, provided that the BCP is overlapped with administration of an agonist (e.g. Lupron, Buserelin, Superfact) for several days leading up to the start of menstruation and the initiation of ovarian stimulation cycle with gonadotropin drugs. If the latter precaution is not taken, and the cycle of stimulation is initiated coming directly off the BCP the response will often be blunted and subsequent egg quality could be adversely affected.
The explanation for this is that in natural (unstimulated) as well as in cycles stimulated with fertility drugs, the ability of follicles to properly respond to FSH stimulation is dependent on their having developed FSH-responsive receptors . Pre-antral follicles (PAF) do not have such primed FSH receptors and thus cannot respond properly to FSH stimulation with gonadotropins. The acquisition of FSH receptor responsivity requires that the pre-antral follicles be exposed to FSH, for a number of days (5-7) during which time they attain “FSH-responsivity” and are now known as antral follicles (AF). These AF’s are now able to respond properly to stimulation with administered FSH-gonadotropins. In regular menstrual cycles, the rising FSH output from the pituitary gland insures that PAPs convert tor AF’s. The BCP (as well as prolonged administration of estrogen/progesterone) suppresses FSH. This suppression needs to be countered by artificially causing blood FSH levels to rise in order to cause PAF to AF conversion prior to COS commencing, otherwise pre-antral-to –antral follicle conversion will not take place in an orderly fashion and the follicles will not readily respond to gonadotropins (FSH) , thereby delaying follicle development by up to 7 days and compromising egg quality. GnRH agonists (e.g. Lupron, Buserelin, Superfact) , cause an immediate surge in release of FSH by the pituitary gland thus causing conversion from PAF to SAF. This is why, women who take a BCP to launch a cycle of COS need to have an overlap of the BCP with an agonist.
By overlapping the BCP with an agonist for a few days prior to menstruation the early recruited follicles are able to complete their developmental drive to the AF stage and as such, be ready to respond appropriately to optimal ovarian stimulation. Using this approach, the timing of the initiation of the IVF treatment cycle can readily and safely be regulated and controlled by varying the length of time that the woman is on the BCP.

The older a woman becomes, the more likely it is that her eggs will be chromosomally/genetically “incompetent” (not have the potential upon being fertilized and transferred, to result in a viable pregnancy). That is why, the likelihood of failure to conceive, miscarrying and of giving birth to a chromosomally defective child (e.g. with Down Syndrome) increases with the woman’s advancing age. In addition, as women age beyond 35Y there is commonly a progressive diminution in the number of eggs left in the ovaries, i.e. diminished ovarian reserve (DOR). So it is that older women as well as those who (regardless of age) have DOR have a reduced potential for IVF success. Much of this is due to the fact that such women tend to have increased production of LH biological activity which can result in excessive LH-induced ovarian male hormone (predominantly testosterone) production which in turn can have a deleterious effect on egg/embryo “competency”.
While it is presently not possible by any means, to reverse the age-related effect on the woman’s “biological clock, certain ovarian stimulation regimes, by promoting excessive LH production (e.g. short agonist/Lupron- “flare” protocols, clomiphene and Letrozole), can 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 older women and those 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 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, http://www.DrGeoffreySherIVF.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?
• 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
I invite you to arrange to have a Skype or an in-person consultation with me to discuss your case in detail. If you are interested, please contact Julie Dahan, at:

Email: Julied@sherivf.com

OR

Phone: 702-533-2691
800-780-7437

I also suggest that you access the 4th edition of my book ,”In Vitro Fertilization, the ART of Making Babies”. It is available as a down-load through http://www.Amazon.com or from most bookstores and public libraries.

reply
Macy

Dear Dr. Sher,

Thank you . I am posting my question again.

I will really appreciate of you could answer my three questions regarding embryo transfer. I am 41 years old and my husband is 39 years old. I had four IVFs.
Previous cycles:
First IVF: Two 5-day embryo transferred- twin pregnancy and then miscarried at 7 weeks. Chromosomal testing female normal embryo.
Second IVF: 3 days embryo transfer- negative
Pooling cycles: (frozen embryoes)
Third IVF: one 7-cell 3-day embryo frozen. Uneven growth of cells.
Fourth IVF : Three 3-day embryo frozen, one has 4 cells (divided evenly), Two are 6 cells (one of 6 cell embryoes dividing evenly)

Since my lining is not responding well to estradiol tablets I will be doing natural cycle. Lining is better in natural cycle. Earlier, I had endometrial receptivity assay done for natural cycle.
My questions:
1) Embryoes from my fourth cycle were slow growing. On third day morning all three embryoes were just 4 cells. In afternoon two made to six cells and were frozen.What causes slow growth of embryo? Can they still implant and make healthy baby?
2) My doctor is recommending to thaw all four embryoes, grow them for two days and then transfer them. If I do what doctor says, then how can growth of all four embryoes can be synchronized if they have different number of cells?
3) How would you recommend transferring them? Day 3 or grow and transfer at day 5.

I would be grateful to you if you could please answer my questions. Thank you.

Macy

reply
Dr. Geoffrey Sher

First, I would strongly advise against a NC IVF at your age. The success rate is likely to be <5% per cycle.

I do agree with your doctor's decision to grow your cleaved embryos out to the blastocyst stage because failure to reach that stage ibn culture points to the embryo being abnormal chromosomally anyway...and not being capable of propagating a viable pregnancy. I would transfer the blastocysts on day 5-6.

In my experience, embryos less than 6 cells cleaved by day 3 of fertilization are usually abnormal and will not make blastocysts or a viable pregnancy.

Older women as well as those who (regardless of age) have diminished ovarian reserve (DOR) tend to produce fewer and less “competent” eggs, the main reason for reduced IVF success in such cases. The compromised outcome is largely due to the fact that such women tend to have increased LH biological activity which often results in excessive LH-induced ovarian testosterone production which in turn can have a deleterious effect on egg/embryo “competency”.
Certain ovarian stimulation regimes either promote excessive LH production (e.g. short agonist/Lupron- “flare” protocols, clomiphene and Letrozole), augment LH/hCG delivered through additional administration (e.g. high dosage menotropins such as Menopur), or fail to protect against body’s own/self-produced LH (e.g. late antagonist protocols where drugs such as Ganirelix/Cetrotide/Orgalutron that are first administered 6-7 days after ovarian stimulation has commenced).
I try to avoid using such protocols/regimes (especially) in older women and those with DOR, favoring instead the use of a modified, long pituitary down-regulation protocol (the agonist/antagonist conversion protocol-A/ACP) augmented by adding supplementary human growth hormone (HGH). I further recommend Staggered IVF with embryo banking of PGS (next generation gene sequencing/NGS)-normal blastocysts in such cases. This type of approach will in my opinion, optimize the chance of a viable pregnancy per embryo transfer procedure and provide an opportunity to capitalize on whatever residual ovarian reserve and egg quality still exists, allowing the chance to “make hay while the sun still shines”.
I strongly recommend that you visit http://www.DrGeoffreySherIVF.com. Then go to my Blog and access the “search bar”. 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 Aproach
• 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.
• 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?
• 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
• Implications of “Empty Follicle Syndrome and “Premature Luteinization”
• Premature Luteinization (“the premature LH surge): Why it happens and how it can be prevented.

Please call or email Julie Dahan, my patient concierge. She will guide you on how to set up an in-person or Skype consultation with me. You can reach Julie at on her cell phone or via email at any time:
Julie Dahan
• Email: Julied@sherivf.com
• Phone: 702-533-2691
 800-780-7437

Geoff Sher

I also suggest that you access the 4th edition of my book ,”In Vitro Fertilization, the ART of Making Babies”. It is available as a down-load through http://www.Amazon.com or from most bookstores and public libraries.
Geoff Sher

reply
Macy

Dear Dr. Sher,
I am sorry, I may have posted this earlier but I can not find the link to my post. so posting again, I will really appreciate if you can consider this.

I will really appreciate of you could answer my three questions regarding embryo transfer. I am 41 years old and my husband is 39 years old. I had four IVFs.
Previous cycles:
First IVF: Two 5-day embryo transferred- twin pregnancy and then miscarried at 7 weeks. Chromosomal testing female normal embryo.
Second IVF: 3 days embryo transfer- negative
Pooling cycles: (frozen embryoes)
Third IVF: one 7-cell 3-day embryo frozen. Uneven growth of cells.
Fourth IVF : Three 3-day embryo frozen, one has 4 cells (divided evenly), Two are 6 cells (one of 6 cell embryoes dividing evenly)

Since my lining is not responding well to estradiol tablets I will be doing natural cycle. Lining is better in natural cycle. Earlier, I had endometrial receptivity assay done for natural cycle.
My questions:
1) Embryoes from my fourth cycle were slow growing. On third day morning all three embryoes were just 4 cells. In afternoon two made to six cells and were frozen.What causes slow growth of embryo? Can they still implant and make healthy baby?
2) My doctor is recommending to thaw all four embryoes, grow them for two days and then transfer them. If I do what doctor says, then how can growth of all four embryoes can be synchronized if they have different number of cells?
3) How would you recommend transferring them? Day 3 or grow and transfer at day 5.

I would be highly grateful to you if you could please answer my questions. Thank you.

Macy

reply
Dr. Geoffrey Sher

I have already resonded earlier today to this post macy. Please look for this.

Geoff Sher

reply
Macy

Dear Dr. Sher, Thank you for your prompt reply. Sorry, I did not bookmarked the page where I posted my message and I can not find your answer. I appreciate your time and really want to know your opinion on my situation. I will appreciate if you could post your message or the link to your answer here. Sorry for any inconvenience. Thank you .
Macy

reply

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