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.
Hello, Dr. Sher,
Will ICSI cause higher probability of congenital abnormalities or rare disease?
Thank you!!
Intracytoplasmic Sperm Injection ICSI which began in 1992 as a treatment for severe male factor infertility, involves the direct injection of a single sperm into each egg under direct microscopic vision.
Soon after the turn of the 20th century it was reported that while the diagnosis of a male factor infertility had remained static, the use of ICSI had markedly increased and that indications for ICSI had expanded from solely male infertility (for which it had primarily been developed) to a wide variety of other indications such as “unexplained infertility, unexplained IVF failure, polycystic Ovarian Syndrome (PCOS) and cases where the woman’s eggs had become more resistant to conventional fertilization. ICSI was also being used in cases where sperm was absent (or virtually absent) from the ejaculate due to congenital or traumatic or medically acquired obstruction of the main collecting ducts (vasa deferentia), testicular failure and in cases where for traumatic, neurologic, or psychologi reasons (impotency) no semen/sperm was being ejaculated. In such cases, sperm obtained through Testicular Sperm Extraction (TESE), or aspiration (TESA) was being successfully used for ICSI. Today in the United states more than 70% of all IVF fertilizations are being conducted using ICSI with high fertilization and pregnancy rates being reported, regardless of sperm concentration, motility or morphology.
Clearly ICSI is increasingly replacing conventional insemination due to its many benefits and lack of definable drawbacks. In fact, pregnancy rates achieved by this method of fertilization are at least as high as those of conventional IVF performed in cases of non-male-factor infertility. Indeed, ICSI is associated with high fertilization and pregnancy rates regardless of sperm concentration, motility or morphology.
Notwithstanding, the above, the proposition that ICSI be preferentially used as the routine method for fertilizing eggs in IVF continues to meet with resistance. Die hards argue that about 1-3% of pregnancies resulting from ICS are associated with congenital developmental and genetic defects that affect the offspring. They cite conditions such as *Beckwith-Wiedemann syndrome, *Angelman syndrome, *hypospadias, sex chromosome abnormalities, a slightly increased miscarriage rate and the fact that male offspring resulting fom ICSI pregnancies are themselves at risk of subsequently developing male infertility in later life.
What you do not often hear from nay-sayers is that those studies that site the above mentioned risks do not distinguish between cases where ICSI is/was mandated for male infertility )and cases where ICSI is/was done for other (non-male infertility) reasons. If this was done, what in my opinion would emerge is that the above mentioned birth defects and developmental conditions are largely confined to the underlying male factor for which ICSI was indicated and are not due to the ICSI process itself. In fact a relatively recent study performed in Sweden demostrated this well. Here 542 children who were conceived naturally were compared with 941 children conceived through IVF (440 by conventional IVF & 541via ICSI) The babies/children were assessed at birth and during the first 5 years of life: The findings revealed that while the incidence of birth and developmental defects was indeed higher in ICSI babies, this only applied to cases where ICSI had been done for male infertility. It did not apply to cases where ICSI was done in the absence of male factor infertility.
Another very important consideration that supports the routine fertilization of eggs by ICSI is the fact that good quality IVF relies heavily on an ability to adequately assess egg maturation immediately following egg retrieval. To do this requires removal of layers of cumulus oophoris (CO) cells that cover the egg envelopment (zona pellucida). Only after the CO is stripped can the 1st polar body (PB-1) which is located immediately under the zona pellucida be identified and it is the presence of PB-1 signifies that indicates that the egg has gone through meiosis (reproductive division) and is thus mature (M2) and overwhelmingly, successful fertilzation and viable embryo development requires that the fertilized egg was mature (M2). This assessment for the presence of PB-1 cannot be reliably done without first removing the cumulus oophoris cells attached to the outer surface of the zona pellucida. The problem is that stripping the cumulus oophoris cells away, markedly reduces natural fertilization potential, leaving ICSI as the only alternative by which to subsequently achieve viable embryo propagation. The only way by which to avoid fertilization by ICSI would be to bypass the important step of assessing egg maturation and this in my opinion would compromize IVF outcome significantly. Thus optimization of the entire IVF process virtually mandates routine ICSI in IVF.
For the above reasons, I proudly count myself among a growing majority of IVF practitioners who support the routine use of ICSI for all IVF patients
*Angelman syndrome is a complex genetic disorder characterized by delayed development, intellectual disability, speech impairment, and problems with movement and balance (ataxia). Most cases are not inherited, particularly those caused by a deletion in the maternal chromosome 15 or by paternal uniparental disomy. These genetic changes are random events that take place during the formation of reproductive cells (eggs and sperm) or in early embryonic development.
Geoff Sher
Hi Dr. Sher,
I am in the process of doing a Natural Cycle FET and just took my Ovidrel last night (May 9). I am scheduled for my transfer on May 15th. My clinic told me to start Prometrium today, 2 in the morning and 2 in the evening, vaginally. I explained to them on the day I found out my last FET failed, that I wanted no meds at all. I’ve had terrible experiences with taking the medication, both vaginally and orally. Is it absolutely necessary for me to take the Progesterone for 5 days before my FET?? My lining was almost 10 mm yesterday, I just don’t see the point.
Thank you for your time
Maria
In my opinion, progesterone should ideally be used for 6 days prior to FET.
Geoff Sher
Is it safe to transfer monosomy chromosome 7 with 30% abnormality according to your opinion?
Regards,
Sandra
Yes, I do believe it is safe.
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 aneuploid embryos 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.” As stated, some 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 considerable clinical value. And would provide a strong argument in favor of preserving certain aneuploid embryos for future dispensation.
Aneuploidy, involves the addition (trisomy) or subtraction (monosomy) of one chromosome in a given pair. As previously stated, some aneuploidies are meiotic in origin while others are mitotic “mosaics”. Certain aneuploidies involve only a single, chromosome pair (simple aneuploidy) while others involve more than a single pair (i.e. complex aneuploidy). Aside from monosomy involving absence of the y-sex chromosome (i.e. XO) which can resulting in a live birth (Turner syndrome) all monosomies involving autosomes (non-sex chromosomes) are lethal and will not result in viable offspring). Some autosomal meiotic aneuploidies, especially trisomies 13, 18, 21, can progress to viable, but severely chromosomally defective babies. All other meiotic autosomal trisomies will almost invariably, either not attach to the uterine lining or upon attachment, will soon be rejected. All forms of meiotic aneuploidy are irreversible while mitotic aneuploidy (“mosaicism) often autocorrects in the uterus. Most complex aneuploidies are meiotic in origin and will almost invariably fail to propagate viable pregnancies.
There is presently no microscopic or genetic test that can reliable differentiate between meiotic and mitotic aneuploidy. Notwithstanding this, the fact that some “mosaic” embryos can autocorrect in the uterus, makes a strong argument in favor of transferring aneuploid of embryos in the hope that the one(s) transferred might be “mosaic” and might propagate viable healthy pregnancies. On the other hand, it is the fear that embryo aneuploidy might result in a chromosomally abnormal baby that has led many IVF physicians to strongly oppose the transfer of any aneuploid embryos to the uterus.
While certain meiotic aneuploid trisomies (e.g. trisomies 13, 18, & 21) can and sometimes do result in chromosomally defective babies, no other meiotic autosomal trisomies can do so. Thus the transfer of trisomic embryos in the hope that one or more might be mosaic, should exclude the use of embryos with trisomies 13, 18 or 21. Conversely, no autosomal monosomic embryos are believed to be capable of resulting in viable pregnancies, thereby making the transfer of autosomally monosomic embryos, in the hope that they are “mosaic”, a far less risky proposition. Needless to say, if such action is being contemplated, it is absolutely essential to make full disclosure to the patient (s) , and to insure the completion of a detailed informed consent agreement which would include a commitment by the patient (s) 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.
Geoff Sher
Hello Doctor, I am 41 years old and trying to conceive my first child… a child I am dying to create a family. My husband and I started late in our marriage to try for kids, I had an abortion at 19 (8 weeks) with my husband (at the time by boyfriend). We naturally got pregnant at age 37.5 but miscarried at 8 weeks. We also had 1 failed IUI at age 39. Sperm analysis I was told was fine – no issues communicated to me to think otherwise. After examining my blood work, I was told that my Amy and fish numbers are just way out of line and due to my age I have a 5% chance if that of conceiving on my own (high FSH anywhere from 19.5 to 27.5). After months of emotionally dealing with the fact that we were going to gave to use donor eggs, I found the strength to proceed. In the Fall of 2017 (age 40), we purchased donor frozen eggs (6) from the clinic’s bank, 4 fertilized and on day 5 no blastocysts, only 2 grade CSU that they decided to transfer in which I was told that they could blastocyst later day inside me or the next day ,…and that studies in Europe showed that grade C had could produce live births. Nothing resulted from this transfer. In April 2018, now 41 age, we were advised to use a fresh ivf cycle donor. We bought a program with another recipient couple to split the fresh donor’s eggs retrieved. The donor produced 19 eggs, of which the other couple received 9 eggs, and we 10. We only fertilized 4eggs, and had 1 make it to blastocyst grade A I was told. We decided on PGS testing of that 1 embryo, and to our devastation came back s abnormal and could not be transferred. I was told the psg results were 49 chromosomes xx missing choosing #7,? It definitely was not a mosaic I was told and co7ld not be transferred. Because the other recipient couple fertilized 7 of their 9 eggs and I believe created 2 (if not 3) embryos but did not have PGS testing I was told, my doctor thinks we could have a sperm issue. This is not what I want to possibly hear at all right now considering I finally got comfortable with understanding my poor quality eggs could never be a part of this process/my child, At this point in time, my doctor recommended if we can afford later to try again with another fresh donor, possibly we could buy donor sperm as well, and have some eggs fertilized with my husband Soren and some with donor sperm to see outcome. I honestly don’t know how to proceed. We will most likely have to take a loan to try again, and I would definitely never do frozen eggs again as I’ve read not much success with that route (which I had more education early on during our journey to save that money). I want to do everything we can to determine if we have chromosomal issues with my husbands sperm, before many any more plans. If we had created note embryos to be tested I would feel more comfortable with a diagnosis that something could be wrong with my husband sperm. But I honestly do not know. Please tell me what you recommend we do to determine this ? I would really like to know we tried every test etc we could to rule out his sperm, before deciding how we would proceed with creating a family? Do we need to see a urologist? Thank you so much for your time.
Hello Doctor. At present I am undergoing IVF treatment. I have given my complete case details below. I got married 5 years back. My age is 33 now.
> Oct 2013 – Normal pregnancy [Urine test positive], but miscarried in one month
> Mar 2015 – Was pregnant again normally, HCG was positive in Apr but no heart beat in June month and used Ziototec Tablet to clear
> Nov 2016 – First IUI – Negative urine test
> Dec 2016 – Second IUI – Negative Urine Test
> Jan 2016 – Third IUI – Negative Urine Test
> Jan 14 2018 – First IVF – HCG was postive after two weeks
First HCG – 199, second HCG – 357, third HCG – 1253, Estrogen – 217.4, Progestrone – 7.7
but Miscarried on Feb 6
> Apr 14 2018 – Second IVF – HCG was postive after two weeks
First HCG – 463, second HCG – 1508, Estrogen – 224, Progestrone – 7
but Miscarried on Apr 29
Both my IVF cycles is performed using Day 5 Blastocyst embroyo transfer. Only one embroyo is transfered for both the cycles since the embroyos are chromosomally checked using PGS method. Embroyos category – First IVF B5AA, second IVF B5AB
We thought it will be successful through IVF as we preferred all the highly possible options. So would like to know what may be causing this problem? What kind of tests i need to perform to diagnose problems if any. I would like to check in all aspects before getting ready for my 3rd transfer. Please advise me on the same. Thanks.