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IVF: The first Choice for Infertile Women 40 to 43 Years of Age

by Dr. Geoffrey Sher on August 29, 2016

Consider the fact that between 40 and 43 of age, the success rate per cycle of treatment with injectible fertility drugs alone, with or without intrauterine insemination (IUI) is 2- 3%. Since it is 6-8 times higher with “conventional” With “conventional IVF” it follows that for such infertile for whom the biological clock is “ticking” IVF is the treatment of choice.

In most cases, an embryo’s “competence” (its potential to propagate a normal pregnancy) is determined by the chromosomal integrity (ploidy) of the egg, rather than the sperm that fertilizes it. Age progressively increases the incidence of abnormal numerical chromosomal egg integrity (aneuploidy) from about 50% in the early 30’s to >80% by the time the woman reaches her 40’s. To make matters worse, most women ages over 40 years of age develop diminishing ovarian reserve (DOR) as evidenced by rising basal FSH and declining blood AMH levels. This results from the decline in ovarian egg population, which once it drops below a certain threshold level and accompanied by an increased incidence in dysfunctional ovulation, a progressive resistance to fertility drugs, a lower yield of eggs/follicles in response to fertility drugs and growing vulnerability to “suboptimal” protocols for ovarian stimulation. Simply stated, unless the protocol used for ovarian stimulation is carefully individualized, women over 40Y and those who (regardless of age) have DOR, will be more likely to propagate chromosomally normal (euploid) eggs that upon fertilization are capable of implanting and propagating normal offspring. To add to the problem, there is nothing that can be done to mitigate this age-related decline.

Thus, the only way to increase the overall likelihood of successful IVF in older women is to:

  1. Individualize (“customize”) the ovarian stimulation protocol so as to meet individual needs avoiding a “same size fits all” approach,
  2. Improve availability of and access to of embryos available by cryobanking or stockpiling “competent” embryos, selected through preimplantation genetic screening (PGS), using reliable testing such as next generation gene sequencing (NGS), over several cycles and then selectively transferring one or two at a time to the uterus in later cycles (i.e. “staggered IVF”).

Unfortunately many infertile women in their 40’s, make the mistake of deliberately deferring the decision to do IVF until they have tried less expensive alternatives such as ovarian stimulation with or without IUI. In the process they often ignore the fact that the differential does not lie in the cost of a procedure. Rather it is lies in the cost of having a baby and it comes in the form of emotional as well as financial currency. The unfortunate reality is that once on the move the biological clock can unfortunately not be reset. Thus in my opinion infertile women of 40-43 years of age (and especially those who have never had a baby before) should consider doing IVF preferentially from the get-go.

For women over 43 years, where fewer than one in ten of their eggs are likely to be euploid, IVF with egg donation is in my opinion, the treatment of choice.

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  • Catherine - October 18, 2017 reply

    Dr Ster,

    I’m a healthy 43 yr old woman who has never been pregnant. I was diagnosed with DOR at age 36. Not surprisingly, it has increased with age. I tried 3 IUI attempts soon after my initial diagnosis. Due to some life events, IVF was not in the cards for awhile. I considered some other options but then decided to save up and plan for IVF with donor eggs. I am part of a plan to be able to do 3 cycles. I begin my first cycle next week. Can you give me an overall assessment (generally speaking) of likelihood for success?

    Thanks

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - October 18, 2017 reply

    At 43y with DOR, the chance of success with own eggs is low…probably under10% for a single conventional IVF cycle. Egg donation would be preferred. However, under certain circumstances it can be significantly improved. read on:

    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?
    • 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

    If you are interested in seeking my advice or services, I urge you to contact my concierge, Julie Dahan ASAP to set up a Skype or an in-person consultation with me. You can also contact Julie by phone or via email at 702-533-2691/ Julied@sherivf.com You can also apply online at http://www.SherIVF.com .

    *FYI
    The 4th edition of my newest book ,”In Vitro Fertilization, the ART of Making Babies” is available as a down-load through http://www.Amazon.com or from most bookstores and public libraries.

    Geoffrey Sher MD

  • infertility clinics in hyderabad - April 27, 2017 reply

    You did a great job that you sharing and provide such a great information about this site. Thank you so much for sharing the best posts they amazing. I am very impressed with your site it’s very interesting one.
    http://www.ivfadvanced.com/

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - April 27, 2017 reply

    Thank you!

    Geoff Sher

  • Nicola Mccauley - November 18, 2016 reply

    Dear Dr Sher,
    I am soon to be 41, husband 44 & we have male factor infertility. I have had 2 failed cycles at the age of 40. I have an AMH of 12.8 when tested last year & have always had good embryo quality or so they say. We are contemplating a 3rd but worried to continue on the same protocol. Any advice would be great…thankyou Nicola

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - November 18, 2016 reply

    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?
    • 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
    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.

  • Lisa - September 14, 2016 reply

    Dear Dr Shear
    I’m 43, turning 44 April next year. No children from before. Ovarian reserves good. AMH level 12.23 ng/ml. Not polycystic. Started oval stimulation, but the more I read the more in doubt. For women at my age chances are about 5% to conceive, right?

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - September 14, 2016 reply

    The 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. Much of this is due to the fact that older 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.

    I try to avoid using such protocols/regimes (especially) in older women , favoring instead the use of a 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
    • Anti Mullerian Hormone (AMH) Measurement to Assess Ovarian Reserve and Design the Optimal Protocol for Controlled Ovarian Stimulation (COS) in IVF.
    • 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
    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.

  • Tess - September 1, 2016 reply

    Dr Sher what are your thoughts on Acupunture and IVF? It is quite expensive to do twice weekly as they suggest on top of the IVF costs! I have read that there is success in having Acupunture done immediately before and after transfer, so I’m considering it. Your thoughts & experience? Is it worth a try?

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - September 1, 2016 reply

    Acupuncture involves the insertion of thin needles into the skin along so called meridians (energy channels). It has been used in China for centuries to regulate and treat many health disorders including ailments involving the female reproductive system.
    When I visited China in 1987, I actually witnessed a Cesarean birth being performed without sedation, pain killers or anesthesia… using only acupuncture. The mother lay there relaxed, conversing with the surgeon and nurses while the surgery was being performed. It was truly quite amazing. So, I need no convincing that this complimentary treatment actually works when used for the right indications.
    The last twenty years has witnessed a virtual explosion in fascination with and interest in acupuncture (as well as in traditional Chinese Herbal Medicine) in Western societies. The growing fascination and interest in the “mystical” power of acupuncture to enhance fertility potential and its incorporation into the IVF arena should come as no surprise, given the desperation of many infertile couples to have a baby. As a consequence, interest in acupuncture has grown by leaps and bounds in the field of Assisted Reproduction in the last 10 to 15 years.
    So,……does acupuncture actually improve IVF outcome? Well, those who support its use as a complementary treatment for IVF claim that it works by improving blood flow to the woman’s reproductive organs and thereby can improve follicle development , egg quality and implantation. But what are the true facts in this regard? Does acupuncture actually enhance reproductive blood flow as has been asserted and if so, does treatment actually improve results? Well, what we do know, based on ultrasound studies, is that acupuncture can indeed enhance uterine blood flow. But convincing evidence that it improves ovarian blood flow is lacking.
    A few years ago, an SIRM doctor reported on the fact that acupuncture administered around the time of embryo transfer improves embryo implantation potential and thus IVF success. Its use during stimulation with fertility drugs has as yet not been shown to improve ovarian follicle growth, egg quality or endometrial thickening. .
    In fairness… acupuncture is not harmful and most of those so treated, swear by it. For the nay-sayers, what can be said with certainty is that at the very least acupuncture has a “feel good” aspect to it and in most, evokes a psychological benefit that should not be discounted.

    In conclusion…..I offer my patients access to in-house acupuncture. But I only recommend that it be administered surrounding the time of embryo transfer, preferably on the day that the embryos are placed in the uterus. However, I caution them intensively not to have exaggerated expectations regarding the role that this complementary therapy might play in enhancing IVF outcome.

    I hope this helps!

    Geoff Sher

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