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.
Dr. Sher,
For an FET, what is the max number of days of Estrace you recommend before starting Progesterone?
I started Estrace on CD4. Today will be day 17 on Estrace (CD20). If my ovaries are still quiet, is there such a thing as going too long on Estrace or too long in your cycle that would compromise the FET success?
I feel a few extra days of Estrace could help me get to a more optimal lining but don’t want to go outside of cycle norms.
Thank you!
I do not use oral estrogens such as Estrace , on my patients. My preference is parenteral estradiol valerate (Delestrogen). In my opinion it is a far better method. Either way, although 17 days is a long time (the average is 9-11 days, it probably wont have a profound effect on outcome.
Frozen Embryo Transfer (FET) A frozen embryo transfer cycle is initiated by administering an oral contraceptive (OC) to the recipient. This is later overlapped with Lupron daily for 5-6 days. The OC is then withdrawn, but the daily Lupron injections are continued until the onset of menstruation. Next, the Lupron dosage is reduced and intramuscular (IM) estradiol valerate (Delestrogen) is administered every 3 days. The objective of the estradiol is to achieve and sustain an optimal plasma E2 concentration of 500pg/ml-1000pg/ml and a 9mm endometrial lining as assessed by ultrasound examination. Intramuscular and/or intravaginal progesterone is administered daily starting about 6 days prior to the FET and continued along with twice weekly IM Delestrogen until the 10th week of pregnancy or until it has been confirmed that the patient is not pregnant.
Daily oral dexamethasone commences with the Lupron start and continues until a negative pregnancy test or until the completion of the 8th week of pregnancy. Then it is tapered down and discontinued. The recipient also receives prophylactic oral antibiotics starting with the initiation of Progesterone therapy, until the day after ET. Usually we would thaw vitrified blastocysts with the objective of having 1, 2 or 3 for transfer; depending on a couple’s stated preference. Commencing on the day following the ET, the patient inserts a vaginal progesterone suppository daily and this is continued until the completion of the 8th week of pregnancy or until a negative pregnancy test.
As an alternative regimen for women who cannot tolerate intramuscular Progesterone (PIO), we prescribe either Crinone vaginal gel or Endometrin vaginal inserts according to protocol. If you’d like to explore one of these options, talk to your physician. For blastocyst FET’s, the blood pregnancy tests are performed 13 days and 15 days after the first progesterone administration is commenced.
Geoff Sher
For an FET, do elevated E2 levels result in decreased success rates?
This study claims that elevated E2 results in lower live births/ongoing pregnancies. Results show that those with peak E2 (135-214 pg/mL) have 54.6% LB/OP rate versus those with peak E2 (692-1713 pg/mL) had a 9.1% LB/OP rate.
https://www.fertstert.org/article/S0015-0282(17)30163-2/fulltext
You advocate for 500-1000 pg/mL for FET. What is the reason for this and do you have a cutoff E2 in which you would cancel a transfer cycle?
Thanks for your expertise!
hi.i am 40 years old. i have 2 , day 3 mosaic monosomy 3 and mosaic trisomy 5 embryos (ngs results).we will transfer the monosomy 3 one. bur what about yhe other. do u reccomend us to transfer the other with the monosomic one. or shall we transfer it if the first fails.help please.
As long as the monosomy does not involve sex chromosomes (XY), they could all be mosaics.
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 preimplantation embryo development, and represents a major cause of early pregnancy loss. About a decade ago, I and an associate, Levent Keskintepe PhD 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 practical 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 aneuploid embryos to the uterus.
Certain meiotic aneuploid trisomy embryos (e.g. trisomies 13, 18, & 21) can and sometimes do, result in aneuploid concepti. Thus, in my opinion, unless the woman/couple receiving such embryos is willing to commit to terminating a resulting pregnancy found through amniocentesis or chorionic villus sampling (CVS) to be so affected, she/they are probably best advised not to transfer such embryos. Other autosomal trisomy embryos will hardly ever produce viable euploid concepti and can thus, in my opinion be transferred in the hope that auto correction will occur in-utero. However, in all cases, and amniocentesis or CVS should be performed to make certain that the baby is euploid. Conversely, no autosomal monosomy embryos are believed to be capable of resulting in viable pregnancies, thereby making the transfer of autosomal monosomy embryos, in the hope that they are “mosaic”, a far less risky proposition. Needless to say, if such action is being contemplated in any such cases, 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 (amniocentesis/CVS) 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
Hi Dr Sher
Is it necessary to do the ACA( anticardiolipin/ antiphospolipid), thyroid hormone, and autoimmune tests before FET( frozen embryo transfer)?
Is it safe to do hepatitis B vaccine as well?
Regards,
Silvia
ACA is a totally inadequate way (in my opinion) to test antiphospholipid antibodies (APA). It only comprises about 6% of APA. You need a total panal of all 21 AP:A’s. The most important when it comes to implantation are antibodies to phosphoserine and phosphoethanolamine. While it is probably not really harmful, I would personally not do the vaccine.
Geoff Sher
dear dr geoffrey sher I forgot to mentions that my anti tpo 800 -900 four 15 yeaars and it was aroud 2000 last year. maybe it is because of miscarriage or use of etrofem for transfer . I dont now. nowaday it is 864 maybe it is because i have been taking selenium 200mg for4 monts
That is a high level.
Geoff Sher
I have hashimoto’s and my blood naturual killers high (if is is meaningfull because it’s not from uterus)Ive convinced my doctor to apply intralipid threatment. he was going to start the infusion just 5 day before fet.and apply ever 3times(on test day and at 12 weeks) then I sent him your article about when to start. I am a bit confused
I will start progesterone on my 15th day of cycle
my first question is which day shoul i have first intralipid infusion. (1 week before progesterone or 2 weeks before progesterone or 2 weeks before FET indepenfent from progesterone)
and which one should I have :intralipid of %10 500ml or %20 250 ml or %20 500ml
second question when we decided to use intralipid, my doctor decided not to use prednisolone together because he think it will to heavy to use them together. he doesnt want to give harm to immunsystem. he said there is no scientific work for using them together.my previous treatment I took prednisolone (deltacortil) 3*5mg for 5 days before FET
I am reading everywhere that prednisolone and ivf together is usefull and it is ok
so
in your oinion
shoul I take 5mg or 10mg or 20mg prednisolone just before FET for 5 days. or from begining of my period to until 12 weeks
or until pregniancy test
what is your way of practice
please help me. i really appreciate your articles
i depend on and trust your practise and your advice
(sorry about my english
my firs ivf 1 embrio of 8 cells failed
then my spontane pregnancy 8,5week heartbeat stoped
an myom occured 2,5cm I had laparoscopy and histereskopy waited for 4 months for recover of uterus
then my second ivf with 3aa and 5aa blast 2 embrios betahcg was 6.43 on 11th day so it’s failed)
If the NK cell activity (not blood concentration alone) is increased by the K-562 target cell blood test or by cytokine measurement of an endometrial biopsy, it is my practice to start IL infusions, 10 days to 2 weeks prior to ET and repeat this with the detection of a +ve pregnancy tedst + to combine such treatment with dexamethasone o.75mg orally daily till the 10th week of pregnancy .
Geoff Sher