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.
For repeated implantation failure, one of your recommendations is some immune tests which I copy below.
I am 38 year old female, with one failed extraction behind me. I would like to try out all these tests but at the same time, also go for another fresh round of extraction. Would my protocol for extraction be different if any of the below tests came out with a abnormal value? In other words, could I get an extraction done, take a pause from the treatment.. do the immune tests and go back to FETs to put the embryos in?
Thanks so much.
a)Antiphospholipid antibody (APA) panel
b)Antinuclear antibody (ANA) panel
c)Antithyroid antibody panel (i.e., antithyroglobulin and antimicrosomal antibodies)
d)Reproductive immunophenotype
e)Natural killer cell activity (NKa) assay (i.e., K562 target cell test)
f)Alloimmune testing of both the male and female partners
It should not alter the stimulation protocol.
The implantation process begins six or seven days after fertilization of the egg. At this time, specialized embryonic cells (i.e., the trophoblast), which later becomes the placenta; begin growing into the uterine lining. When the trophoblast and the uterine lining meet, they, along with Immune cells in the lining, become involved in a “cross talk” through mutual exchange of hormone-like substances called cytokines. Because of this complex immunologic interplay, the uterus is able to foster the embryo’s successful growth. Thus, from the very earliest stage of implantation the trophoblast establishes a foundation for the future nutritional, hormonal and respiratory interchange between mother and baby. In this manner, the interactive process of implantation is not only central to survival in early pregnancy but also to the quality of life after birth.
Considering its importance, it is not surprising that failure of proper function of this immunologic interaction during implantation has been implicated as a cause of recurrent miscarriage, late pregnancy fetal loss, IVF failure, and infertility. A partial list of immunologic factors that may be involved in these situations includes anti-phospholipid antibodies (APA), antithyroid antibodies (ATA), and most importantly activation of uterine natural killer cells (NKa). Presently, these immunologic markers in the blood can be only adequately measured by a handful of highly specialized reproductive immunology laboratories in the United States. I personally use Reproductive Immunology Associates in Van Nuys, CA or Reprosource in Boston, MA.
The Central role of Natural Killer cells: After ovulation and during early pregnancy, NK cells comprise more than 70% of the immune cell population of the uterine lining. NK cells produce a variety of local hormones known cytokines. Uncontrolled, excessive release of certain cytokines (i.e. TH-1 cytokines) is highly toxic to the trophoblast (“root system”) of the embryo” leading to their programmed death (apoptosis) and, subsequently to failed or compromised/dysfunctional implantation. In the following situations NK cells become activated, and start to produce an excess of TH-1 cytokines:
•Autoimmune Implantation Dysfunction: This is most commonly seen in association with a personal or family history of autoimmune diseases such as ith conditions such as Rheumatoid arthritis, hypothyroidism endometriosis and Lupus Erythematosus, Scleroderma, Dermatomyositis etc. It is also encountered in one third of women who have endometriosis (regardless of its severity), and in cases of “unexplained infertility” as well as with recurrent pregnancy loss (RPL).
•Alloimmune implantation dysfunction where the male and female partners share specific genetic (DQ-alpha and/or HLA) similarities This is commonly seen in cases of RPL and in cases of secondary infertility
Activated NK cells (NKa) can be detected through the K-562 target cell blood test and (more recently) through uterine biopsy for TH-1 cytokine activity. Treatment involves selective use of Intralipid (IL) or immunoglobulin (IVIG) therapy combined with oral steroids, initiated more 10-14 days prior to embryo transfer and in most cases of alloimmune implantation dysfunction, the transfer of a single blastocyst at a time.
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:
•The Role of Immunologic Implantation Dysfunction (IID) & Infertility (IID):PART 1-Background
•Immunologic Implantation Dysfunction (IID) & Infertility (IID):PART 2- Making a Diagnosis
•Immunologic Dysfunction (IID) & Infertility (IID):PART 3-Treatment
•Thyroid autoantibodies and Immunologic Implantation Dysfunction (IID)
•Immunologic Implantation Dysfunction: Importance of Meticulous Evaluation and Strategic Management:(Case Report
•Intralipid and IVIG therapy: Understanding the Basis for its use in the Treatment of Immunologic Implantation Dysfunction (IID)
•Intralipid (IL) Administration in IVF: It’s Composition; How it Works; Administration; Side-effects; Reactions and Precautions
•Natural Killer Cell Activation (NKa) and Immunologic Implantation Dysfunction in IVF: The Controversy!
•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
•How Many Embryos should be transferred: A Critical Decision in IVF.
•Endometriosis and Immunologic Implantation Dysfunction (IID) and IVF
•Endometriosis and Infertility: Why IVF Rather than IUI or Surgery Should be the Treatment of Choice.
•Endometriosis and Infertility: The Influence of Age and Severity on Treatment Options
•Early -Endometriosis-related Infertility: Ovulation Induction (with or without Intrauterine Insemination) and Reproductive Surgery Versus IVF
•Treating Ovarian Endometriomas with Sclerotherapy.
•Effect of Advanced Endometriosis with Endometriotic cysts (Endometriomas) on IVF Outcome & Treatment Options.
•Deciding Between Intrauterine Insemination (IUI) and In Vitro Fertilization (IVF).
•Intrauterine Insemination (IUI): Who Needs it & who Does Not: Pro’s &
•Induction of Ovulation With Clomiphene Citrate: Mode of Action, Indications, Benefits, Limitations and Contraindications for its ue
•Clomiphene Induction of Ovulation: Its Use and Misuse!
If you are interested in my advice or medical services, 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.
Also, my book, “In Vitro Fertilization, the ART of Making Babies” is available as a down-load through http://www.Amazon.com or from most bookstores and public libraries.
Hi Dr Sher, my amh is 11.1 pmol and in my last round of IvF I had 12 follicles but unfortunately it was unsuccessfuL that was using 225 gonal f. This time my doctor has suggested a long protocol as follows
1. On Day 22 start injecting Diphereline 0.1 mg subcutaneously into your belly in the MORNING every day!
2. From day 1 of your bleeding please start injecting Menopur 75 IU 3 ampules daily subcutaneously into your belly in the MORNING and continue injecting the Diphereline!
3. Plan US scan for day 6, 7, OR 8 of your stimulation – asking for endometrium and number of follicles and diameters – locally
Another clinic has suggested a short protocol again doing similar to last time with some tweaks.
My questions are
1. Should there be BCP in this protocol ?
2. Would you recommend gonal f and menopur mix (225 / 75) instead of just menopur
Does everything else seem okay? Any red flags you can see.
In this instance would you prefer a long or short protocol
Thank you for your help
Thank you, what do you think about long protocol without the use of BCP ?
You mention two labs on your webpage (1) Reproductive Immunology Associates (2) Reprosource. Do you prefer one over the other for the following tests for repeated implantation failure?
a)Antiphospholipid antibody (APA) panel
b)Antinuclear antibody (ANA) panel
c)Antithyroid antibody panel (i.e., antithyroglobulin and antimicrosomal antibodies)
d)Reproductive immunophenotype
e)Natural killer cell activity (NKa) assay (i.e., K562 target cell test)
f)Alloimmune testing of both the male and female partners
I use Reprosource, but in my opinion, both are good. And yes, both can do all the tests you stipulate.
Geoff Sher
Dr. Sher,
I recently did my fifth ivf.
I sent out three blast for PGS.
I have one normal girl, one with trisomy 20 and another with -19 and -21.
I am waiting for my mosiac report.
My RE said both abnormals would be okay to transfer.
I am seeking your advise.
Hello Dr. Sher,
I am a 38 year old female, married and tried one IVF extraction unsuccessfully. I made 19 eggs and 9 embryos made it to the Blastocyst stage. We did not do any PGS on the embryos before implantation. 7 embryos have been put in and no implantation happened.
I have not used any birth control in my life. I am a non-smoker and non-drinker. My karotype analysis did not reveal anything abnormal and I do not carry any genetic mutations (which are testable). I have never been pregnant before.
My AMH is 4.54 ng/ml (test range: 0.176 to 11. 7 ng/ml).
My TSH is 0.77mIU/L (reference range 0.44- 3.98).
I was tested for Prolactin Serum, Anticardiolipin Ab, Beta 2 glycoprotein Ab with nothing out of the ordinary.
My husband has good enough sperm count (50 million/ml). Total motile sperm is 12-50 million.
At the beginning of the extraction, I was told that I was a good candidate for IVF. My infertility specialist thinks I should go for another round of extraction. But she tells me that since I made 9 blastocysts, she would not change my stimulation protocol. But would instead recommend PGS on the embryos.
My husband and I are engineers…So may be we are looking at this in the wrong way. If an experiment fails (My IVF extraction and repeated implantation failure (RIF)); how can you do the same experiment again and expect a different result?
I have sought a second, third opinion and no doc wants to change my Stimulation protocol.
Your thoughts?
Thanks very much
Hello Dr. Sher,
I am a 38 year old female, married and tried one IVF extraction unsuccessfully. I made 19 eggs and 9 embryos made it to the Blastocyst stage. We did not do any PGS on the embryos before implantation. 7 embryos have been put in and no implantation happened.
I have not used any birth control in my life. I am a non-smoker and non-drinker. My karotype analysis did not reveal anything abnormal and I do not carry any genetic mutations (which are testable). I have never been pregnant before.
My AMH is 4.54 ng/ml (test range: 0.176 to 11. 7 ng/ml).
My TSH is 0.77mIU/L (reference range 0.44- 3.98).
I was tested for Prolactin Serum, Anticardiolipin Ab, Beta 2 glycoprotein Ab with nothing out of the ordinary.
My husband has good enough sperm count (50 million/ml). Total motile sperm is 12-50 million.
At the beginning of the extraction, I was told that I was a good candidate for IVF. My infertility specialist thinks I should go for another round of extraction. But she tells me that since I made 9 blastocysts, she would not change my stimulation protocol. But would instead recommend PGS on the embryos.
HSG and hysteroscopy were normal. My uterine lining before transfer hovers around 8 mm. No uterine polyps or fibroids.
My husband and I are engineers…So may be we are looking at this in the wrong way. If an experiment fails (My IVF extraction and repeated implantation failure (RIF)); how can you do the same experiment again and expect a different result?
I have sought a second, third opinion and no doc wants to change my Stimulation protocol.
Your thoughts?
Thanks very much