Ask Our Doctors – Archive
Our Medical Directors are outstanding physicians that you will find to be very personable and compassionate, who take care to ensure that you have the most cutting-edge fertility treatments at your disposal. This is your outlet to ask your questions to the doctors.
I’m 41, undergoing ivf for fertility preservation before starting 5-10 years of tamoxifen. Goal is to have viable embryos to freeze (donor sperm). My first cycle resulted in 11 retrieved, 7 mature, and 2 fertilized. The embryologist recommends ICSI next round. (There were additional eggs fertilized, but abnormally.) My RE suggested HGH next cycle, and this is what I’m concerned about. My cancer was hormone receptor positive (ER+ and PR+), HER2 negative. No lymph node involvement. Would 4-5 days of HGH be horrible? I would be taking letrozole as well.
I asked RE if I can start tamoxifen now and take 2 months to improve egg quality with supplements before cycle #2. She will be asking at the big office meeting on Wednesday. Seems like a false choice to weigh immediate cycle #2 with HGH versus delaying hormone therapy in hopes of boosting egg quality naturally.
Thank you for making yourself available for questions, and for the extensive resources here!
I do not think HGH for such a short period of time will place you at any risk!
I am not in favor of using Letrozole or clomiphene-type medications (e.e., Tamoxifin) around the time of stimulation as it increases LH-release and can cause ovarian follicular testosterone levels to increase to a level that it can compromise egg quality.
It is primarily the egg (rather than the sperm) that determines the chromosomal integrity (karyotype) of the embryo, the most important determinant of egg/embryo competency”. A “competent” egg is therefore one that has a normal karyotype and has the best potential to propagate a “competent” embryo. In turn, a “competent embryo is one that possesses the highest potential to implant and develop into a normal, healthy, baby.
When it comes to reproductive performance, humans are the least efficient of all mammals. Even in young women under 35y, at best only 1 out of 2 eggs are chromosomally numerically normal (euploid). The remained have an irregular number of chromosomes (aneuploid) and are thus “incompetent”. The incidence of egg aneuploidy increases with age such by age 39 years, 3 in 4 are competent, and by the mid-forties, less 8 to 9 out of 10 are aneuploid. The fertilization of an aneuploid egg will inevitably lead to embryo aneuploid and an aneuploid embryo cannot propagate a normal pregnancy
Within hours of the spontaneous pre-ovulatory luteinizing hormone (LH) surge, and also following administration of the human chorionic gonadotropin (hCG) “trigger” shot (given to induce ovulation after ovarian stimulation with fertility drugs), the egg embarks on a rapid maturational process that involves halving of its 46 chromosomes to 23. During this process, (known as meiosis) 23 chromosomes are retained within the nucleus of the egg while the remaining (now redundant) 23are expelled, enveloped by a thin membrane. This small structure comes to lie immediately below the “shell” of the egg (the zona pellucida) and is known as the 1st polar body or PB-1. The spermatozoon, in the process of its maturation also undergoes meiosis at which time it too reduces its chromosomes by half. Thus in the process of fertilization the sperm divides into two separate functional gametes, each containing 23 chromosomes such that with subsequent fertilization, the 23 chromosomes in the egg, fuse with the 23 chromosomes of the mature sperm resulting in the development of an embryo that has 46 chromosomes (the normal human genome) comprising a combination of the genetic material from both partners. For the embryo to have exactly 46 chromosomes (the euploid number), both the mature egg and mature spermatozoon must contain exactly 23 chromosomes. Only euploid embryos are “competent” (capable of developing into healthy babies). Those with an irregular number of chromosomes (aneuploid embryos) are “incompetent” and are incapable of developing into healthy babies. While embryo “incompetence” can result from either egg or sperm aneuploidy, it usually stems from egg aneuploidy. However, in cases of moderate or severe male factor infertility, the sperm’s contribution to aneuploidy of the embryo increases significantly.
While embryo ploidy (numerical chromosomal integrity) is not the only determinant of its “competency, it is by far the most important and in fact is rate-limiting factor in human reproduction. It is causal in most cases of “failed implantation” which in turn is responsible for most cases of failed IVF. It causes early miscarriages and is responsible for many chromosomal birth defects such as X-monosomy and Down’s syndrome. . In most cases, embryos that develop too slowly as well as those that grow too fast (i.e. ones that by day 3 post-fertilization comprise fewer than 6 cells or more than 9 cells) and/or embryos that contain a large amount of cell debris or “fragments” are usually aneuploid and are thus “incompetent”. Additionally, embryos that fail to survive in culture to the blastocyst stage are also almost always aneuploid/”incompetent”. At a certain point in the later stage of a woman’s reproductive career, the number of remaining eggs in her ovaries falls below a certain threshold, upon which she is unable to respond optimally to fertility drugs. Often times this is signaled by a rising day 3 blood follicle stimulating hormone (FSH) level. Such women with diminishing ovarian reserve produce fewer eggs in response to ovarian stimulation. While diminished ovarian reserve is most commonly encountered in women over 40 years of age it can and indeed sometimes does occur in much younger women. A few important (but often overlooked concepts should be considered in this regard: 1. Age: It is advancing chronologic age and NOT declining ovarian reserve (as evidenced by abnormal blood AMH or FSH that results in an increased incidence of egg/embryo “incompetence” due to aneuploidy 2. DOR: The ovaries and developing eggs of women with diminished ovarian reserve (regardless of age) are highly susceptible to the adverse effect of excessive Luteinizing Hormone (LH)-induced overproduction of male hormones (mainly testosterone). A little testosterone produced by the ovary promotes normal follicle growth and orderly egg development but too much testosterone has the opposite effect. That is why (especially in women with diminished ovarian reserve who often have high LH and increased ovarian testosterone production , the use of ovarian stimulation protocols that fail to down-regulate LH production prior to initiating stimulation with gonadotropins, often prejudices egg/embryo quality and IVF outcome. Simply stated, while age is certainly the most important factor in determining the incidence of egg/embryo aneuploidy, women with diminished ovarian reserve (regardless of their age), unless they receive customized/individualized protocols of ovarian stimulation are less likely to propagate euploid (competent) eggs/embryos.
Selection of the ideal protocol for controlled ovarian stimulation: While NOTHING can be done to lower the incidence of age related aneuploidy, it is indeed possible to avoid a further increase in egg/embryo aneuploidy by individualizing the protocols of ovarian stimulation used.
•My preferred protocols for women who have relatively normal ovarian reserve:
a)The conventional long pituitary down regulation protocol: BCP are commenced early in the cycle and continued for at least 10 days. Starting 3 days before the BCP is to be discontinued, it is overlapped with an agonist such as Lupron 10U daily for three (3) days and continued until menstruation begins (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. Simultaneously, the Lupron dosage is reduced to 5U daily and an FSH-dominant gonadotropin such as Follistim, Puregon or Gonal-f daily is commenced for 2 days. On the 3rd day the gonadotropin dosage is reduced and a small amount of daily menotropin (Menopur 75U daily) is added. Daily ultrasound and blood estradiol measurements are done starting on the 7th or 8th day of gonadotropin administration and continued until daily ultrasound follicle assessments indicate that most follicles have fully developed. At this point egg maturation is “triggered” using an intramuscular injection of 10,000U hCG. And an egg retrieval is scheduled for 36h later.
b)The agonist/antagonist conversion protocol (A/ACOP): This is essentially the same as the conventional long down regulation protocol (as above), except that with the onset of post-BCP menstruation, the agonist is supplanted by daily administration of a GnRH antagonist (e.g. Ganirelix, Cetrotide or Orgalutron) at a dosage of 125mcg daily until the day of the hCG trigger
•My preferred protocol for women who have relatively diminished ovarian reserve (DOR):
When it comes to women who have DOR I favor the use of the A/ACP, adding supplementary human growth hormone (HGH). In some cases where the DOR is regarded as severe, I also augment the process with estrogen priming, preferring twice weekly intramuscular administration of estradiol valerate (Delestrogen), starting with the commencement of antagonist injection and continuing for 1 week before commencing gonadotropins and continued until the hCG “trigger. I further recommend that such women be offered access to preimplantation genetic screening (PGS) for4 embryo selection and in some cases, for embryo banking (stockpiling). This is followed in a later hormone replacement cycle with the selective transfer of up to two (2) PGS-normal, euploid blastocysts. In this way we are able to capitalize on whatever residual ovarian reserve and egg quality might still exist and thereby “make hay while the sun still shines” , significantly enhancing the opportunity to achieve a viable pregnancy
•The following Ovarian stimulation protocols are in my opinion best avoided in women with DOR:
a)Microdose agonist (e.g. Lupron) “flare” protocols
b)High doses of LH/hCG-containing fertility drugs (E.G. Menopur).
c)Protocols that incorporate supplementation with male hormones (e.g. testosterone)
d)Supplementation with DHEA
e)Clomiphene citrate or Letrozole which cause an elevation in LH and thus increase ovarian male hormone (testosterone and androstenedione output.
f)“Triggering” egg maturation using too low a dosage of hCG (e.g. 5,000U rather than 10,000U) or Ovidrel e.g. 250mcg of Ovidrel rather than 500mcg)
g)“Triggering” women who have large numbers of follicles using an agonist such as Lupron, Superfact or Buserelin.
•Preimplantation Genetic Screening (PGS):
The introduction of preimplantation genetic screening (PGS) for the first time permits identification of all the chromosomes in the egg and embryo such that we can now far better identify “competent” (euploid) embryos for selective transfer to the uterus. This vastly improves the efficiency and success of the IVF process. This additional tool has better equipped us to manage cases with DOR. In my opinion, next generation gene sequencing (NGS), currently represents the most reliable method for performing PGS
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).
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Geoff Sher
ace
Hi Doctor.
My Hcg levels are like this
28381 – May 27th, 2021
27426 – May 23, 2021
23528 – May 20, 2021
14876 – May 13, 2021
3673 – May 6th, 2021
460 – April 30th, 2021
I booked scan on june 1st as its the latest availability. I am concerned as the numbers look indifferent. Is this a good sign? Should i wait until then or go to emergency?. Please reply.
Thanks
I am a little concerned about the pattern of your hCG rise. Your upcoming ultrasound should be conclusive.
Good luck!
Geoff SDher
Dear Dr. Sher, do you have any doctors in the UK who you have ever worked with before who would be happy to consider following one of your protocols? I would love to have a Skype consultation with you, but there is no point if I cannot then find a clinic in the UK who could carry out some of what you recommend. Thank you!
Sorry Laura,
I do not!
Geoff Sher
Do you perform IVM? I have PCOS and have a history of blood clots so less estrogen exposure in my mind would be better. Thoughts?
In my opinion IVM has no real merit;
Geoff Sher
I am 32 and my husband is 36. I was actually a patient of your back in 2012 and you gave us a little miracle boy on the first IVF (using intralipid IV infusions) with you after 6 failed IVF’s prior (including an ectopic resulting in my tube being removed and preterm delivery of twins at 5 months). You did testing and found that I had an MTHFR gene mutation as well as my husband and I being a partial DQalpha match. My husband and I have been together for almost 15 years and have never used protection and have not gotten pregnant without the assistance of fertility treatment. Well, last week I was absolutely shocked to found out that as of today I am 6 weeks and 2 days pregnant. When I found out at 5 weeks and 4 days my HCG was at 4,000 (drawn at the ER). I have not had any other blood draws yet until I can get into my OB. They could see a yok sac in a stomach ultrasound (done on Wednesday), and will be going for a transvaginal ultrasound here soon. I know we had talked to you a little about if ever we got pregnant naturally what are the chances of it being a viable pregnancy that would last until term, but we also knew it was a VERY slim chance I every would get pregnant naturally. I do not remember exactly your thoughts on it, so I wanted to ask you about it. Is an HCG level of 4,000 at 5 weeks 4 days, a good sign? There was no fetal pole visible on the on the 5 week 4 day transvaginal ultra sound done at the ER. Is that normal? They could see the yok sack though, and when I went to an ultrasound place on Wednesday everything was still growing and the yok sack was visible on the stomach ultrasound. My biggest question is, what do you think the chances of the pregnancy going to term is? Do you think there is a high chance of a miscarriage? Also, my husband was wondering if we should be thinking about doing any gene testing or anything to make sure it is okay? I told him I thought I remember you saying if there was a gene mutation (which you all checked for being the day 5 transfer) that the embryo would not have made it anyways to start a pregnancy, but I wasn’t sure, so wanted to ask that too. Sorry for all the questions, but thank you so much for your time and always caring so much about your patients!!!!
Congratulations! I am so happy for you. It goes to show…miracles can and do happen because “man proposes and G-d disposes”.
At this stage the numbers look good but it is too late to intervene with additional therapies for an immunologic issue. So, you need to wait it out and see how things go!
Good luck and G-d bless
Geoff Sher
P>S: Please keep me in the loop!