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Human Growth Hormone Administration in IVF: Does it Enhance Egg/Embryo Quality and Outcome?

by Dr. Geoffrey Sher on March 4, 2016

The term “Biological Clock” is used to define the time line for  a woman’s reproductive potential. It is affected primarily by two factors:

  1. Age:  Advancing age is inevitably accompanied by a progressive reduction in the number of eggs in the ovaries (“ovarian reserve”). With progressive diminution in ovarian reserve (DOR) a theoretical “threshold” is reached where the woman’s response to fertility drugs is markedly reduced. At the point that this results in a low yield in follicles and eggs, she is referred to as being a “poor responder” to ovarian stimulation. DOR is accompanied by a fall in blood AMH levels and a rise in basal blood FSH. Over time a progressive reduction in ovarian reserve will ultimately culminate in a cessation of ovulation and menstruation (i.e. the menopause).
  2. Egg “Competency” The second component of the biological clock is an inevitable age-related decline in egg competency (the ability of an egg, upon fertilization, to propagate a healthy embryo that is capable of propagating a normal baby) . The most important manifestation of this age-related occurrence, is an inevitable and rapid increase in the percentage of “incompetent” eggs that have numerical chromosome irregularities (aneuploidy). By way of example: at age 30Y, about one out of two human eggs will be incompetent/aneuploid while at 45Y more than nine out of ten are so afflicted. Aneuploid eggs cannot propagate healthy babies. Most will not even fertilize and those that do will usually be lost as early miscarriages or infrequently will survive and go on to produce a chromosomally defective child (e.g. Down syndrome).

It is important to understand that the two components of the biological clock (i.e. ovarian reserve and age) represent variables which while interrelated, can often exist independently. By way of example: some older women in their mid-forties have excellent ovarian reserve while some women in their thirties may have DOR. While such women will produce fewer eggs, the potential competency of the eggs they produce is largely tied to their age. For example, a microscopically normal looking mature egg from a 30 year old woman is probably 3 times more likely to be “competent” similar looking egg derived from a 40 year old counterpart.  The ovarian hormonal environment elicited through ovarian stimulation of a woman with DOR can be affected by the protocol used for ovarian stimulation. Selecting the wrong stimulation protocol can adversely influence egg competency. Conversely, an individualized and optimal protocol for ovarian stimulation, by favorably regulating the ovarian hormonal environment, can improve the potential for optimal follicle and egg development in the very same person, thereby reducing the risk of egg aneuploidy. The problem is that it becomes progressively more difficult to optimally regulate the intra-ovarian hormonal environment in older women, and in those with DOR. It is in such cases that the use of human growth hormone can play a valuable role.

Several researchers have shown that the administration of human growth hormone (HGH), given as an adjunct to ovarian stimulation, enhances follicle response in older women and those with DOR and so can help optimize egg quality. It is thought that HGH hormone by increasing the production of insulin-like growth factor 1 (IGF-1), improves follicle development, estrogen hormone production and egg maturation. Two basic mechanisms have been proposed: 1) improving the response to gonadotropin therapy by up-regulating the FSH receptors on the granulosa cells that form the inner lining of follicles and, 2) through a direct enhancing effect of HGH on the egg’s mitochondrial activity.  While human eggs do have HGH receptors, those retrieved from older women show decreased expression of such receptors (as well as a reduction in the number of functional mitochondria) when compared with those derived from younger counterparts. In fact, it has recently been shown that older women treated with HGH showed a marked increase in functional mitochondria in their eggs along with improved egg quality.

My own experience in selectively prescribing HGH as an adjuvant, to women with DOR, older women and those with unexplained egg quality deficits, is that if used in combination with customized and individualized protocols of ovarian stimulation it can indeed enhance egg/embryo quality and ovarian response, culminating in improved IVF outcome.

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  • Melissa - July 21, 2017 reply

    Thank you for sharing this info! My current RE just told me that HGH is only helpful in people with DOR. I’m reading otherwise here, that it can also help egg quality and the mitochondrial energy in eggs in older patients, correct?

    I am 42, have PCOS, hypothyroid, and mthfr. My first IVF cycle I had 22 eggs, 17 fertilized, 6 day 5-6 blasts tested, but only 1 PGS normal (which implanted, but was a blighted ovum). My protocol was 225 Follistim and 225 menopur for days 1-11, Ganarelix for a few days, and a 5000iu pregnyl trigger.

    My next cycle is planned in 2 months for 450 Follistim, 150 menopur, cetrotide, and Lupron trigger.

    What are your thoughts on the protocol change, but more so, your thoughts on adding in HGH to help quality? Thank you!

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - July 21, 2017 reply

    You seem to have responded well so the dosage of gonadotropins does not seem to be an issue. I do not believe in such a high dosage of menotropins (Menopur) given the high hCg/LH content. I also do not agree with a “Lupron trigger”, see below.

    Ideal egg development sets the scene for optimal egg maturation that occurs 36-42h prior to ovulation or egg retrieval. Without prior optimal egg development (ovogenesis), egg maturation will be dysfunctional and most eggs will be rendered “incompetent” and unable upon fertilization to propagate viable embryos. In IVF, optimal ovogenesis requires the selection and implementation of an individualized approach to controlled ovaria stimulation (COS). Thereupon, at the ideal time, maturational division of the egg’s chromosomes (i.e. meiosis) is “triggered” through the administration of hCG or an agonist such as Lupron, which induces an LH surge. The, dosage and timing of the “trigger shot” profoundly affects the efficiency of meiosis, the potential to yield “competent (euploid) mature (M2) eggs, and as such represents a rate limiting step in the IVF process .

    “Triggering meiosis with Urine-derived hCG (Pregnyl/Profasi/Novarel) versus recombinant hCG (Ovidrel): Until quite recently, the standard method used to “trigger” egg maturation was through the administration of 10,000 units of hCGu. Subsequently,, a DNA recombinant form of hCGr (Ovidrel)was introduced and marketed in 250 mcg doses. But clinical experience strongly suggests that 250 mcg of Ovidrel is most likely not equivalent in biological potency to 10,000 units of hCG. It probably only has 50%-70%of the potency of a 10,000U dose of hCGu and as such might not be sufficient to fully promote meiosis, especially in cases where the woman has numerous follicles. For this reason, I firmly believe that when hCGr is selected as the “trigger shot” the dosage should best be doubled to 500 mcg at which dosage it will probably have an equivalent effect on promoting meiosis as would 10,000 units of hCGu. Failure to “trigger” with 10,000U hCGu or 500mcg hCGr, will in my opinion increase the likelihood of disorderly meiosis, “incompetent (aneuploid) eggs” and the risk of follicles not yielding eggs at egg retrieval (“empty follicles”). Having said this, it is my personal opinion that it is unnecessary to supplant hCGu with hCGr since the latter is considerably more expensive and is probably no more biopotent than the latter.

    Some clinicians, when faced with a risk of OHSS developing will deliberately elect to reduce the dosage of hCG administered as a trigger in the hope that by doing so the risk of critical OHSS developing will be lowered. It is my opinion, that such an approach is not optimal because a low dose of hCG (e.g., 5000 units, hCGu or 250mcg hCGr) is likely inadequate to optimize the efficiency of meiosis particularly when it comes to cases such as this where there are numerous follicles. It has been suggested that the preferential use of an “agonist (Lupron) trigger” in women at risk of developing severe ovarian hyperstimulation syndrome could potentially reduce the risk of the condition becoming critical and thereby placing the woman at risk of developing life-endangering complications. It is with this in mind that many RE’s prefer to trigger meiosis by way of an “agonist (Lupron) trigger rather than through the use of hCG. The agonist promptly causes the woman’s pituitary gland to expunge a large amount of LH over a short period of time and it is this LH “surge” that triggers meiosis. The problem with using this approach, in my opinion, is that it is hard to predict how much LH will be released in by the pituitary gland. For this reason, I personally prefer to use hCGu for the trigger, even in cases of ovarian hyperstimulation hyperstimulated, with one important proviso…that being that is she underwent “prolonged coasting” in order to reduce the risk of critical OHSS, prior to the 10,000 unit hCGu “ trigger”.

    The timing of the “trigger shot “to initiate meiosis: This should coincide with the majority of ovarian follicles being >15 mm in mean diameter with several follicles having reached 18-22 mm. Follicles of larger than 22 mm will usually harbor overdeveloped eggs which in turn will usually fail to produce good quality eggs. Conversely, follicles less than 15 mm will usually harbor underdeveloped eggs that are more likely to be aneuploid and incompetent following the “trigger”.

    Here is the protocol I advise for women, <40Y who have adequate ovarian reserve.
    My advice is to use a long pituitary down regulation protocol starting on a BCP, and overlapping it with Lupron 10U daily for three (3) days and then stopping the BCP but continuing on Lupron 10u daily (in my opinion 20U daily is too much) and await a period (which should ensue within 5-7 days of stopping the BCP). At that point an US examination is done along with a baseline measurement of blood estradiol to exclude a functional ovarian cyst and simultaneously, the Lupron dosage is reduced to 5U daily to be continued until the hCG (10,000u) trigger. An FSH-dominant gonadotropin such as Follistim, Puregon or Gonal-f daily is started with the period for 2 days and then the gonadotropin dosage is reduced and a small amount of menotropin (Menopur---no more than 75U daily) is added. This is continued until US and blood estradiol levels indicate that the hCG trigger be given, whereupon an ER is done 36h later. I personally would advise against using Lupron in “flare protocol” arrangement (where the Lupron commences with the onset of gonadotropin administration.
    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.
    • The IVF Journey: The importance of “Planning the Trip” Before Taking the Ride”
    • 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
    • Use of GnRH Antagonists (Ganirelix/Cetrotide/Orgalutron) in IVF-Ovarian Stimulation Protocols.
    • Anti Mullerian Hormone (AMH) Measurement to Assess Ovarian Reserve and Design the Optimal Protocol for Controlled Ovarian Stimulation (COS) in IVF.
    • Treating Out-of-State and Out-of-Country Patients at Sher-IVF in Las Vegas
    • Should IVF Treatment Cycles be provided uninterrupted or be Conducted in 7-12 Pre-scheduled “Batches” per Year
    • A personalized, stepwise approach to IVF
    • “Triggering” Egg Maturation in IVF: Comparing urine-derived hCG, Recombinant DNA-hCG and GnRH-agonist:
    ANNOUNCEMENTS:
    1. About my Retirement
    After > 30 years in the field of Assisted Reproduction (AR), the time has finally come for me to contemplate retiring from full-time clinical medicine. If you are interested in my medical services prior to my retirement, 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.

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

    Geoffrey Sher MD

  • Robyn - April 21, 2016 reply

    I turned 40 this week. I have had a molar pregnancy and a chemical pregnancy in the past year. We decided ivf was our best option. I just completed an egg retrieval with no successful embryos. There were three eggs retrieved, two fertilized, and the two did not grow. I have been labeled a “non-responder” . We are considering another egg retrieval with a different protocol. My doctor told me about the benefits of adding human growth hormone to the protocol but says he cannot prescribe it here in the US anymore. I’ve read your research and it seems you are able to give it to your patients. How do I get a prescription? Thank you for all your informative articles. I have learned so much from this blog site. Can I get hgh here in the US?

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - April 22, 2016 reply

    Hi Robyn,

    Your Re will have to advise you on this. Sorry I cannot help. However, this alone is not likely to resolve your problem which likely is linked to diminished ovarian reserve.

    I would use an agonist/antagonist conversion protocol with human growth hormone (HGH) augmentation and would recommend Staggered IVF with embryo banking of PGS (next generation gene sequencing)-normal blastocysts, to make hay while the sun still shines.
    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
    • Ovarian Stimulation for IVF using GnRH Antagonists: Comparing the Agonist/Antagonist Conversion Protocol.(A/ACP) With the“Conventional” Antagonist Aproach
    • IVF: Factors Affecting Egg/Embryo “competency” during Controlled Ovarian Stimulation(COS)
    • 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)
    • 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?
    • 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 Sampling (PGS) Using: Next Generation Gene Sequencing (NGS): Method of Choice.
    • IVF Failure and Implantation Dysfunction: The Role of Endometrial Thickness, Uterine Pathology and Immunologic Factors
    • 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

    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

  • kelly - April 9, 2016 reply

    Hi can I use hgh with femara and ttc naturally. Not with ivf? To increase my chances of getting pregnant? I am 44yrs old. Or is hgh only used in ivf cases

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - April 10, 2016 reply

    You could, but I am not aware of reports using this regime.

    Geoff Sher

  • Tina - March 23, 2016 reply

    You mention personalized protocols for ovarian stimulation. What would be your recommendation for 41 yo. Will be 42 in April. Good ovarian reserve with amh 8.1. Had two Ivf cycles. Used growth hormone second cycle only. First cycle had 3 embryos that made it to day 5. Pgs 2/3 normal genetically. Second cycle 7 embryos biopsied 2/7 normal genetically. Debating third cycle.
    Thanks for the help.

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - March 23, 2016 reply

    I would use a modified, long pituitary down-regulation protocol (an agonist/antagonist conversion protocol with human growth hormone-HGH augmentation) Given your age, I would recommend Staggered IVF with embryo banking of PGS (next generation gene sequencing)-normal blastocysts, to make hay while the sun still shines.

    Please visit my new Blog at o to http://goo.gl/4hvjoP , 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
    • Ovarian Stimulation for IVF using GnRH Antagonists: Comparing the Agonist/Antagonist Conversion Protocol.(A/ACP) With the“Conventional” Antagonist Aproach
    • IVF: Factors Affecting Egg/Embryo “competency” during Controlled Ovarian Stimulation(COS)
    • 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.
    • 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?
    • 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 Sampling (PGS) Using: Next Generation Gene Sequencing (NGS): Method of Choice.
    • IVF Failure and Implantation Dysfunction: The Role of Endometrial Thickness, Uterine Pathology and Immunologic Factors
    • Why did my IVF Fail
    • 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

    I invite you to call 702-699-7437 or 800-780-7437 or go online on this site and set up a one hour Skype consultation with me to discuss your case in detail.

    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
    I invite you to call 702-699-7437 or 800-780-7437 or go online on this site and set up a one hour Skype consultation with me to discuss your case in detail.

    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

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