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.
Hi
My husband and I have three healthy boys. The first two were conceived naturally, the third with the help of Clomid – I conceived on the second round with this. I have never miscarried and always had easy, straight forward pregnancies.
We are desperate for a daughter and have just undergone our first round of IVF with PGS, sadly with no success – all of the female embryos came back abnormal.
11 eggs were retrieved, 10 were fertilised, 8 survived for PGS testing and the results came back as follows:
1 – Complex abnormal – unknown sex
2 – Abnormal +10 FEMALE
3 – Abnormal -16 FEMALE
4 – Normal MALE
5 – Normal MALE
6 – Abnormal +4, -9, +13, -21 FEMALE
7 – Normal MALE
8 – Abnormal -18 Male
The embryologist hinted that we may genetically, never be able to conceive a ‘normal’ daughter, and my world has come crashing down 🙁
We have decided to go for a second round, but I am curious to know your opinion – could this be a simple case of bad luck or would the evidence suggest that he may be right?
Your website and blogs are so informative, it is hard to find such detailed advice online.
If you have time, I very much look forward to hearing from you.
Many thanks
First, I totally disagree that you are incapable of producing female embryos. Second, if I read the chromosomal configuration of your embryos correctly, one was a female monosomy 16. You should know that even though it tested thus, the abnormality could be the result of mosaicism and thus capable of “autocorrecting” after implantation (see below.).
Human embryo development occurs through a process that encompasses reprogramming, sequential cleavage divisions and mitotic chromosome segregation and embryonic genome activation. Chromosomal abnormalities may arise during germ cell and/or pre-implantation embryo development, and represents a major cause of early pregnancy loss. About a decade ago, I and an associate, Levent Keskintepe Ph.D were the first to introduce full embryo karyotyping (identification of all 46 chromosomes) through preimplantation genetic sampling (PGS) as a method by which to selectively transfer only euploid embryos (i.e. those that have a full component of chromosomes) to the uterus. We subsequently reported on a 2-3 fold improvement in implantation and birth rates as well as a significant reduction in early pregnancy loss, following IVF. Since then PGS has grown dramatically in popularity such that it is now widely used throughout the world.
Most IVF programs that offer PGS services, require that all participating patients consent to all their aneuploid embryos (i.e. those with an irregular quota of chromosomes) be disposed of. However, there is now growing evidence to suggest that following embryo transfer, some aneuploid embryos will in the process of ongoing development, convert to the euploid state (i.e. “autocorrection”) and then go on to develop into chromosomally normal offspring. In fact, I am personally aware of several such cases occurring within our IVF network. So clearly , summarily discarding all aneuploid embryos as a matter of routine we are sometimes destroying some embryos that might otherwise have “autocorrected” and gone on to develop into normal offspring.
Thus by discarding all aneuploid embryos we and in so doing, the possibility exists that we could be denying some women the opportunity of having a baby. This creates a major ethical and moral dilemma for those of us that provide the option of PGS to our patients. On the one hand, we strive “to avoid knowingly doing harm” (the Hippocratic Oath) and as such would prefer to avoid or minimize the risk of miscarriage and/or chromosomal birth defects and on the other hand we would not wish to deny patients with aneuploid embryos, the opportunity to have a baby.
The basis for such embryo “autocorrection” lies in the fact that some embryos found through PGS-karyotyping to harbor one or more aneuploid cells (blastomeres) will often also harbor chromosomally normal (euploid) cells (blastomeres). The coexistence of both aneuploid and euploid cells coexisting in the same embryo is referred to as “mosaicism.” Many such mosaic embryos will In the process of subsequent cell replication convert to the normal euploid state (i.e. autocorrect)
It is against this background, that an ever increasing number of IVF practitioners, rather than summarily discard PGS-identified aneuploid embryos are now choosing to cryobanking (freeze-store) certain of them, to leave open the possibility of ultimately transferring them to the uterus. In order to best understand the complexity of the factors involved in such decision making, it is essential to understand the causes of embryo aneuploidy of which there are two varieties:
1.Meiotic aneuploidy” results from aberrations in chromosomal numerical configuration that originate in either the egg (most commonly) and/or in sperm, during preconceptual maturational division (meiosis). Since meiosis occurs in the pre-fertilized egg or in and sperm, it follows that when aneuploidy occurs due to defective meiosis, all subsequent cells in the developing embryo/blastocyst/conceptus inevitably will be aneuploid, precluding subsequent “autocorrection”. Meiotic aneuploidy will thus invariably be perpetuated in all the cells of the embryo as they replicate. It is a permanent phenomenon and is irreversible. All embryos so affected are thus fatally damaged. Most will fail to implant and those that do implant will either be lost in early pregnancy or develop into chromosomally defective offspring (e.g. Down syndrome, Edward syndrome, Turner syndrome).
2.“Mitotic aneuploidy” occurs when following fertilization and subsequent cell replication (cleavage), some cells (blastomeres) of a meiotically euploid early embryo mutate and become aneuploid. This is referred to as mosaicism. Thereupon, with continued subsequent cell replication (mitosis) the chromosomal make-up (karyotype) of the embryo might either comprise of predominantly aneuploid cells or euploid cells. The subsequent viability or competency of the conceptus will thereupon depend on whether euploid or aneuploid cells predominate. If in such mosaic embryos aneuploid cells predominate, the embryo will be “incompetent”). If (as is frequently the case) euploid cells prevail, the mosaic embryo will be “competent” and capable of propagating a normal conceptus.
Since some mitotically aneuploid (“mosaic”) embryos can and indeed do “autocorrect’ while meiotically aneuploid embryos cannot, it follows that an ability to differentiate between these two varieties of aneuploidy would be of enormous clinical value. Since some mosaic embryos can “autocorrect” and even go on to propagate a viable baby, the ability to confirm that aneuploidy is mitotic (potentially reversible) would provide a strong argument in favor of preserving certain aneuploid embryos for future dispensation. Unfortunately however, there is presently no microscopic or genetic test that can reliable differentiate between meiotic and mitotic aneuploidy.
Aneuploidy, whether meiotic or mitotic in origin involves the addition of one or more chromosomes to a given pair in human embryos. Certain aneuploidies involve only a single, chromosome pair (simple aneuploidy) while others involve more than a single pair (i.e. complex aneuploidy). Evidence suggests that complex aneuploidy, whether meiotic or mitotic in origin is almost always lethal while all forms of meiotic aneuploidy are permanent. Some aneuploidies, especially those that involve addition of a chromosome to any pair (trisomy) will at times progress to clinical pregnancies (e.g. trisomy 15, 18, 21 or when the sex chromosomes are involve). And as stated previously, most aneuploid embryos, should they attach, will miscarry or result in a chromosomally defective offspring.
On the other hand, some aneuploid embryos have one chromosome (in a given pair) missing (i.e. monosomy). Aside from monosomy involving absence of the y-sex chromosome (i.e. XO) which can resulting in a live birth (Turner syndrome) all other monosomies involving autosomes (non-sex chromosomes) are lethal and will not result in viable offspring.
Since it is presently not possible, without removing more than 1 cell from an embryo (a very traumatic event) to differentiate between meiotic and mitotic aneuploidy, it follows that making a diagnosis of embryo aneuploidy does not allow for identification of mosaic embryos for transfer. This is especially true when it comes to trisomic embryos that can and sometimes do, propagate chromosomal birth defects such as Down syndrome. It is important to bear in mind that the transfer of trisomic embryos (whether due to meiotic or mitotic aneuploidy) can result in miscarriage or a birth defect. This makes any attempt to transfer such embryos to the uterus such a transfer, fraught with risk and in my opinion, ill advised. Conversely, since true meiotic autosomal monosomic embryos cannot propagate viable pregnancies, performing embryo transfer in such cases in the hope that the aneuploidy is mitotic (mosaic) in origin and will spontaneously “autocorrect”, is a rational consideration. Needless to say, such action would require full disclosure, the completion of a detailed informed consent agreement which would include an expressed commitment to undergo prenatal genetic testing aimed at excluding a chromosomal defect in the developing baby and/or a willingness to terminate the pregnancy should a serious birth defect be diagnosed.
Since it is meiotic rather than mitotic aneuploidy that is invariably lethal and given that meiotic aneuploidy originates in the egg, it is my belief that the closer to fertilization that embryo biopsy is done for PGS, the more likely it is that any aneuploidy detected, will be meiotic in origin. The longer you wait thereafter, the greater the likelihood that with repeated mitotic division, mutational changes will result in mitotic aneuploidy (mosaicism). This is why I strongly believe embryo biopsies should be performed on day 2-3 post fertilization rather on day 5-6 days (the blastocyst stage).”.
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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Thank you so much for getting back to me, your reply has given us hope again and the idea of the embryos ‘autocorrecting’ is indeed very interesting. I wondered what your advice would be with regards to how many embryos we should put back in, in the event that we do get some healthy females? We would really prefer not to have twins but if it increases our odds…?
fsh 13 day 1 if take birth control 14 days then go reevaluate does that help
I do not think it is needed Jeni!
Geoff Sher
Today I am 5 days post a 5 day frozen embryo transfer. The blastocyst was hatching the day of the transfer, which my RE said was excellent. This morning I took a home pregnancy test on First Response Early Result (which I’m told is the most sensitive test on the market). It was negative, not even a faint line. Is it just that it could be too early? I was thinking that since it was hatching, implantation would occur sooner.
It is much too early for the urine test to become +ve. Try 5-7 days from now.
Good luck!
Geoff Sher
Do you think it would be beneficial for me to do a double pregnyl trigger (20,000iu)? I am 35, amh .2, AFC 4. I’ve had one successful cycle and one failed. I’ve read your article on the types of trigger shots and was curious is since I’m such low risk for OHSS if it would help in maturation rates.
I do not believe this would help in any way!
good luck!
Geoff Sher
Dear Dr Sher,
I am 44 but super healthy, I was ID’d for alcohol recently as I look so young! Lifetime of healthy living, no smoking, no alcohol, healthy weight, exercise, vegetarian diet etc. Very regular 28 day cycles with LH surge day 13/14 like clockwork. Last year became pregnant naturally after literally 1 month of trying (and a lifetime of safe sex!), I miscarried at 12+3 (after fetal heart on 7 wk scan), no abnormalities found, suspect severe stress at the time caused immune issues + rejection, now have high peripheral NK cells + CD19.
1 failed IVF Lite, 4 eggs collected from right ovary, all fertilised, 2 made grade A embryo’s, but no pregnancy. Left ovary could not be safely accessed as too high in position. 2nd IVF had to be converted to IUI as most follicles grew on left side, still no pregnancy. Protocol used was Suprecur + 150iu Bemfola for a few days down to 75iu until lead follicle >18mm. Also had intralipids, prednisolone and clexane last cycle (am MTHFR heterozygous), and endometrial scratch.
I’m on 400mg CoQ10, prenatal vitamins with l-methyl folate, omega oils, 1000mg Vit D amongst other things. Have tried 25mg daily DHEA for 6 months, can’t tolerate higher dosage. Don’t know whether to continue with this.
Feeling desperate due to my age. Don’t want donor eggs. Baffled as to why I got pregnant so easily but now can’t again. Partner has great sperm. I know I’m old but could it be the severe stress and grieving from the miscarriage? I’m doing acupuncture and starting yoga to try to combat this.
Please advise how you would treat me. Should I try HGH, if so on what dosage and time schedule? Protocol suggestions please?
With grateful thanks for your reply.
In my opinion, mini (“lite”) IVF, “microdose” (“flare”) Lupron protocols, the use of clomiphene or Letrozole, and high dosage Menopur protocols, should best not be used in women with DOR (see below). It surges LH and with it ovarian testosterone as the stimulation begins and this can have a deleterious effect on egg quality/competency…especially in older women and also in women such as yourself who have DOR. You need a modified, robust, long pituitary down-regulation protocol. 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 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.
•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
•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