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 am dating a Transgender male. I am a female, if we decide to have kids. I’d like to know if it’s possible to freeze some of his eggs (before he fully transitions) use donor semen to fertilize them when we are ready and do the exact same thing with some of my eggs with the same donor semen and implant them into me both at the same time so that I can birth both our babies at the same time.
It could be done but the underlying ethics involved would need to be researched. It would take some research into the feasibility.
Geoff Sher
Dr. Sher,
I am 42 and have had 3 IVF retrievals. I produce many eggs (10-18 in each retrieval) but only one of 6 blasts produced in those 3 retrievals tested as normal. The FET of that embryo failed and the last retrieval resulted in serious complications (internal bleeding) such that I do not think it is wise to do anymore retrievals. I may move on to donor eggs, but may try IUI while thinking about that prospect. I am fully aware of the low odds of IUI, but assuming I do go forward, would you recommend IUI with Clomid and trigger shot OR IUI with injectibles and trigger shot? Thanks.
While I would advise against IUI but I would definitely not use clomiphene at 42y of age3. The success rate will be <2%
Geoff Sher
Hi Dr Sher,
I am 35 with a history of Crohns Disease. I have a son from an IUI 3 years ago, and since have had 4 chemical pregnancies (3 from IUI, 1 from IVF). I have hypothalamic amenorrhea, but I respond EXTREMELY well to stims (almost hyperstimming with every cycle). I almost act like a PCOS patient, but I have a normal FSH. Also, my AMH is 2.3. My IVF cycles always yield a great number of eggs, but the embryo quality is not the greatest. My husbands sperm is pretty much perfect.
My question is…. do you feel I need to be on some sort of immune protocol?? I am currently on 10 mg of prednisone, 75mg of 6-mercaptopurine, and Stelara for my Crohns Disease. Would intralipids be benficial?? Or a higher dose of steroids?? I had an RPL panel done and everything was normal, other than a positive ANA. No clotting issues found. Just wondering if all signs are pointing to an immune implantation problem. My current RE is not a huge believer in immune issues. Any advice would be greatly appreciated. Thanks in advance for taking the time to read this!
Sincerely,
Amy
I would definitely not proceed further without making a major attempt to determine the cause of your losses. In this regard please consider the following:
When it comes to reproduction, humans are the poorest performers of all mammals. In fact we are so inefficient that up to 75% of fertilized eggs do not produce live births, and up to 30% of pregnancies end up being lost within 10 weeks of conception (in the first trimester). RPL is defined as two (2) or more failed pregnancies. Less than 5% of women will experience two (2) consecutive miscarriages, and only 1% experience three or more.
Pregnancy loss can be classified by the stage of pregnancy when the loss occurs:
•Early pregnancy loss (first trimester)
•Late pregnancy loss (after the first trimester)
•Occult “hidden” and not clinically recognized, (chemical) pregnancy loss (occurs prior to ultrasound confirmation of pregnancy)
•Early pregnancy losses usually occur sporadically (are not repetitive).
In more than 70% of cases the loss is due to embryo aneuploidy (where there are more or less than the normal quota of 46 chromosomes). Conversely, repeated losses (RPL), with isolated exceptions where the cause is structural (e.g., unbalanced translocations), are seldom attributable to numerical chromosomal abnormalities (aneuploidy). In fact, the vast majority of cases of RPL are attributable to non-chromosomal causes such as anatomical uterine abnormalities or Immunologic Implantation Dysfunction (IID).
Since most sporadic early pregnancy losses are induced by chromosomal factors and thus are non-repetitive, having had a single miscarriage the likelihood of a second one occurring is no greater than average. However, once having had two losses the chance of a third one occurring is double (35-40%) and after having had three losses the chance of a fourth miscarriage increases to about 60%. The reason for this is that the more miscarriages a woman has, the greater is the likelihood of this being due to a non-chromosomal (repetitive) cause such as IID. It follows that if numerical chromosomal analysis (karyotyping) of embryonic/fetal products derived from a miscarriage tests karyotypically normal, then by a process of elimination, there would be a strong likelihood of a miscarriage repeating in subsequent pregnancies and one would not have to wait for the disaster to recur before taking action. This is precisely why we strongly advocate that all miscarriage specimens be karyotyped.
There is however one caveat to be taken into consideration. That is that the laboratory performing the karyotyping might unwittingly be testing the mother’s cells rather than that of the conceptus. That is why it is not possible to confidently exclude aneuploidy in cases where karyotyping of products suggests a “chromosomally normal” (euploid) female.
Late pregnancy losses (occurring after completion of the 1st trimester/12th week) occur far less frequently (1%) than early pregnancy losses. They are most commonly due to anatomical abnormalities of the uterus and/or cervix. Weakness of the neck of the cervix rendering it able to act as an effective valve that retains the pregnancy (i.e., cervical incompetence) is in fact one of the commonest causes of late pregnancy loss. So also are developmental (congenital) abnormalities of the uterus (e.g., a uterine septum) and uterine fibroid tumors. In some cases intrauterine growth retardation, premature separation of the placenta (placental abruption), premature rupture of the membranes and premature labor can also causes of late pregnancy loss.
Much progress has been made in understanding the mechanisms involved in RPL. There are two broad categories:
1.Problems involving the uterine environment in which a normal embryo is prohibited from properly implanting and developing. Possible causes include:
•Inadequate thickening of the uterine lining
•Irregularity in the contour of the uterine cavity (polyps, fibroid tumors in the uterine wall, intra-uterine scarring and adenomyosis)
•Hormonal imbalances (progesterone deficiency or luteal phase defects). This most commonly results in occult RPL.
•Deficient blood flow to the uterine lining (thin uterine lining).
•Immunologic implantation dysfunction (IID). A major cause of RPL. Plays a role in 75% of cases where chromosomally normal preimplantation embryos fail to implant.
•Interference of blood supply to the developing conceptus can occur due to a hereditary clotting disorder known as Thrombophilia.
2.Genetic and/or structural chromosomal abnormality of the embryo.Genetic abnormalities are rare causes of RPL. Structural chromosomal abnormalities are slightly more common but are also occur infrequently (1%). These are referred to as unbalanced translocation and they result from part of one chromosome detaching and then fusing with another chromosome. Additionally, a number of studies suggest the existence of paternal (sperm derived) effect on human embryo quality and pregnancy outcome that are not reflected as a chromosomal abnormality. Damaged sperm DNA can have a negative impact on fetal development and present clinically as occult or early clinical miscarriage. The Sperm Chromatin Structure Assay (SCSA) which measures the same endpoints are newer and possibly improved methods for evaluating.
IMMUNOLOGIC IMPLANTATION DYSFUNCTION
Autoimmune IID: Here an immunologic reaction is produced by the individual to his/her body’s own cellular components. The most common antibodies that form in such situations are APA and antithyroid antibodies (ATA).
But it is only when specialized immune cells in the uterine lining, known as cytotoxic lymphocytes (CTL) and natural killer (NK) cells, become activated and start to release an excessive/disproportionate amount of TH-1 cytokines that attack the root system of the embryo, that implantation potential is jeopardized. Diagnosis of such activation requires highly specialized blood test for cytokine activity that can only be performed by a handful of reproductive immunology reference laboratories in the United States.
Alloimmune IID, i.e., where antibodies are formed against antigens derived from another member of the same species, is believed to be a relatively common immunologic cause of recurrent pregnancy loss.
Autoimmune IID is often genetically transmitted. Thus it should not be surprising to learn that it is more likely to exist in women who have a family (or personal) history of primary autoimmune diseases such as lupus erythematosus (LE), scleroderma or autoimmune hypothyroidism (Hashimoto’s disease), autoimmune hyperthyroidism (Grave’s disease), rheumatoid arthritis, etc. Reactionary (secondary) autoimmunity can occur in conjunction with any medical condition associated with widespread tissue damage. One such gynecologic condition is endometriosis. Since autoimmune IID is usually associated with activated NK and T-cells from the outset, it usually results in such very early destruction of the embryo’s root system that the patient does not even recognize that she is pregnant. Accordingly the condition usually presents as “unexplained infertility” or “unexplained IVF failure” rather than as a miscarriage.
Alloimmune IID, on the other hand, usually starts off presenting as unexplained miscarriages (often manifesting as RPL). Over time as NK/T cell activation builds and eventually becomes permanently established the patient often goes from RPL to “infertility” due to failed implantation. RPL is more commonly the consequence of alloimmune rather than autoimmune implantation dysfunction.
However, regardless, of whether miscarriage is due to autoimmune or alloimmune implantation dysfunction the final blow to the pregnancy is the result of activated NK cells and CTL in the uterine lining that damage the developing embryo’s “root system” (trophoblast) so that it can no longer sustain the growing conceptus. This having been said, it is important to note that autoimmune IID is readily amenable to reversal through timely, appropriately administered, selective immunotherapy, and alloimmune IID is not. It is much more difficult to treat successfully, even with the use of immunotherapy. In fact, in some cases the only solution will be to revert to selective immunotherapy plus using donor sperm (provided there is no “match” between the donor’s DQa profile and that of the female recipient) or alternatively to resort to gestational surrogacy.
DIAGNOSING THE CAUSE OF RPL
In the past, women who miscarried were not evaluated thoroughly until they had lost several pregnancies in a row. This was because sporadic miscarriages are most commonly the result of embryo numerical chromosomal irregularities (aneuploidy) and thus not treatable. However, a consecutive series of miscarriages points to a repetitive cause that is non-chromosomal and is potentially remediable. Since RPL is most commonly due to a uterine pathology or immunologic causes that are potentially treatable, it follows that early chromosomal evaluation of products of conception could point to a potentially treatable situation. Thus I strongly recommend that such testing be done in most cases of miscarriage. Doing so will avoid a great deal of unnecessary heartache for many patients.
Establishing the correct diagnosis is the first step toward determining effective treatment for couples with RPL. It results from a problem within the pregnancy itself or within the uterine environment where the pregnancy implants and grows. Diagnostic tests useful in identifying individuals at greater risk for a problem within the pregnancy itself include:
•Karyotyping (chromosome analysis) both prospective parents
•Assessment of the karyotype of products of conception derived from previous miscarriage specimens
•Ultrasound examination of the uterine cavity after sterile water is injected or sonohysterogram, fluid ultrasound, etc.)
•Hysterosalpingogram (dye X-ray test)
•Hysteroscopic evaluation of the uterine cavity
•Full hormonal evaluation (estrogen, progesterone, adrenal steroid hormones, thyroid hormones, FSH/LH, etc.)
•Immunologic testing to include:
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
TREATMENT OF RPL
Treatment for Anatomic Abnormalities of the Uterus: This involves restoration through removal of local lesions such as fibroids, scar tissue, and endometrial polyps or timely insertion of a cervical cerclage (a stitch placed around the neck of the weakened cervix) or the excision of a uterine septum when indicated.
Treatment of Thin Uterine Lining: A thin uterine lining has been shown to correlate with compromised pregnancy outcome. Often this will be associated with reduced blood flow to the endometrium. Such decreased blood flow to the uterus can be improved through treatment with sildenafil and possibly aspirin.
Sildenafil (Viagra) Therapy. Viagra has been used successfully to increase uterine blood flow. However, to be effective it must be administered starting as soon as the period stops up until the day of ovulation and it must be administered vaginally (not orally). Viagra in the form of vaginal suppositories given in the dosage of 25 mg four times a day has been shown to increase uterine blood flow as well as thickness of the uterine lining. To date, we have seen significant improvement of the thickness of the uterine lining in about 70% of women treated. Successful pregnancy resulted in 42% of women who responded to the Viagra. It should be remembered that most of these women had previously experienced repeated IVF failures.
Use of Aspirin: This is an anti-prostaglandin that improves blood flow to the endometrium. It is administered at a dosage of 81 mg orally, daily from the beginning of the cycle until ovulation.
Treating Immunologic Implantation Dysfunction with Selective Immunotherapy: Modalities such as IL/IVIg, heparinoids (Lovenox/Clexane), and corticosteroids (dexamethasone, prednisone, prednisolone) can be used in select cases depending on autoimmune or alloimmune dysfunction.
The Use of IVF in the Treatment of RPL
In the following circumstances, IVF is the preferred option:
1.When in addition to a history of RPL, another standard indication for IVF (e.g., tubal factor, endometriosis, and male factor infertility) is superimposed.
2.In cases where selective immunotherapy is needed to treat an immunologic implantation dysfunction.
The reason for IVF being a preferred approach in such cases is that in order to be effective, the immunotherapy needs to be initiated well before spontaneous or induced ovulation. Given the fact that the anticipated birthrate per cycle of COS with or without IUI is at best about 15%, it follows that short of IVF, to have even a reasonable chance of a live birth, most women with immunologic causes of RPL would need to undergo immunotherapy repeatedly, over consecutive cycles. Conversely, with IVF, the chance of a successful outcome in a single cycle of treatment is several times greater and, because of the attenuated and concentrated time period required for treatment, IVF is far safer and thus represents a more practicable alternative
Since embryo aneuploidy is a common cause of miscarriage, the use of preimplantation genetic diagnosis (PGD), with tests such as CGH, can provide a valuable diagnostic and therapeutic advantage in cases of RPL. PGD requires IVF to provide access to embryos for testing.
There are a few cases of intractable alloimmune dysfunction due to absolute DQ alpha matching where Gestational Surrogacy or use of donor sperm could represent the only viable recourse, other than abandoning treatment altogether and/or resorting to adoption. Other non-immunologic factors such as an intractably thin uterine lining or severe uterine pathology might also warrant that last resort consideration be given to gestational surrogacy.
The good news is that if a couple with RPL is open to all of the diagnostic and treatment options referred to above, a live birthrate of 70%–80% is ultimately achievable.
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
•Ovarian Stimulation for IVF using GnRH Antagonists: Comparing the Agonist/Antagonist Conversion Protocol.(A/ACP) With the “Conventional” Antagonist Approach
•Ovarian Stimulation in Women Who have Diminished Ovarian Reserve (DOR): Introducing the Agonist/Antagonist Conversion protocol
•Anti Mullerian Hormone (AMH) Measurement to Assess Ovarian Reserve and Design the Optimal Protocol for Controlled Ovarian Stimulation (COS) in IVF.
•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
•IVF: How Many Attempts should be considered before Stopping?
•“Unexplained” Infertility: Often a matter of the Diagnosis Being Overlooked!
•IVF Failure and Implantation Dysfunction:
•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!
•Endometrial Thickness, Uterine Pathology and Immunologic Factors
•Vaginally Administered Viagra is Often a Highly Effective Treatment to Help Thicken a Thin Uterine Lining
•Treating Out-of-State and Out-of-Country Patients at Sher-IVF in Las Vegas:
•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
If you are interested in seeking my advice or 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 .
*FYI
The 4th edition of my newest 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.
Geoffrey Sher MD
Hi Dr Sher,
I just finished reading your response to Jaqueline’s question as it happened to be somewhat similar to my situation as well. I apologize in advance for my long post, but I’m hoping that the background information will be helpful for you in answering my questions.
My husband and I finally got pregnant through IVF last October after two years of trying unsuccessfully on our own. Unfortunately, the pregnancy ended in a missed miscarriage at about 8 1/2 weeks. With our first pregnancy, the initial HCG shot up quickly and increased quicker than expected [which, surprisingly, prompted our RE to tell us (before our initial ultrasound) that she thought both embryos had implanted]. At our 6 ½ week appointment, we ended up seeing only one embryo with what looked like a strong heartbeat; however we were measuring a couple days behind. It’s possible that both had implanted and that we lost one before the first ultrasound? At 7 1/2 weeks, a different technician did the ultrasound and told us that the baby was “smaller” and the heartbeat was “weaker.” This technician was new to the clinic and had another nurse come in for a second opinion. The second nurse took a look and told us that everything was fine. We ended up leaving the appointment feeling uneasy and confused.
I later emailed our doctor’s assistant for more clarification and we were told that the nurse “was likely referring to the fact that we had a large yolk sac” (this was the first time anyone had mentioned anything about the yolk sac to us). A measurement was never taken of the yolk sac, but based on the ultrasound image that we had, we estimated that it was likely about 5 1/2 to 6cm. Unfortunately, at 8 ½ weeks, a heartbeat was no longer found on the ultrasound. I had a D&C and the chromosomal testing came back as inconclusive since the results said, “female, normal.”
Following our miscarriage, my husband and I decided we wanted to do another round of IVF embryo banking in order to have more embryos on hand before we moved forward with another transfer. Unfortunately, our initial RE was not receptive to alternative methods of starting a cycle other than birth control and we held off moving forward while we explored other clinics in the area.
While we were researching other clinics, we ended up getting pregnant on our own with my first regular period after the miscarriage. We were so surprised! Unfortunately, the HCG did not double as expected and at six weeks only reached the high three hundreds. Sadly, the pregnancy ended in miscarriage at about six weeks (possibly prolonged due to supplementation of progesterone).
My initial bloodwork before starting IVF showed a deficiency in Vitamin D and I have been taking a supplement ever since. I had a thyroid panel done and TSH was found to be slightly elevated (at around 3.0) back in August. I have been on Levothyroxine since and I’ve been told that my TSH tests have all come back good and that I should stay on the same dose for now. I had NK cells and antiphospholipid checked and was told both were normal. Per my PCP’s recommendation (due to family history of strokes), I also had Factor II & V screened and it came back negative. I have been taking 81mg of aspirin daily since before my first embryo transfer.
Before our first round of IVF, we did genetic testing and my husband was flagged as a carrier for cystic fibrosis. Nothing else was noted in the genetic testing. We also recently did karyotype testing for both my husband and myself and the results came back normal.
My husband’s initial SA came back with poor morphology and borderline motility, but after adding supplements for three months, morphology improved and SCSA results showed “Excellent to Good Sperm DNA Integrity” and DFI of 8%.
I am 37 years old, but in general good health. All of my bloodwork came back indicating that I should have had a good response to COS, but I responded poorly to the medications and the doctor wanted to cancel our cycle at the last minute. We decided to move forward with retrieval anyway. I had always been leery of using BCP to start the IVF cycle and still believe that it may have negatively impacted my response to the stimulation medications (thank you for all of your wonderful information on this!), but now I am more concerned about my ability to carry a baby to term due to two miscarriages in a row (one of them following a natural pregnancy). We are set to start a new estrogen priming cycle next month after confirmation of ovulation.
We knew I had an intrauterine obstruction before doing our first round of IVF, but our RE recommended waiting to do the hysteroscopic myectomy until after stimulation since she said that the stimulation hormones could possibly cause polyp or fibroid growth. I had a hysteroscopic myectomy before our first transfer and a polyp was removed. My RE’s office did the saline sonogram after my hysteroscopic myectomy and I was cleared for embryo transfer. I didn’t discover, until after our miscarriage that there was a 3.8cm submucosal fibroid that had not been addressed and was still obscuring the uterine cavity. At this point, my OB also told me that my uterus was enlarged (comparing my uterus to the “size of an orange when it should be the size of a lemon”). At first, I thought that the pregnancy might have caused the fibroid to grow as I knew this was a possibility; however, after reviewing my medical file from my first RE’s office I discovered that the fibroid was there before the transfer and appears to be roughly the same size as before our transfer that led to our first pregnancy (we can see the fibroid in the ultrasound image from the day of our embryo transfer). I’ve been told that I have several smaller intramural fibroids each measuring under 2cm in addition to the submucosal fibroid that last measured around 3.8cm. In your response to Jacquline, you mention that, “Late pregnancy losses….are most commonly due to anatomical abnormalities of the uterus and/or cervix.” I was wondering – can anatomical abnormalities, such as fibroids, also cause first trimester miscarriages as well? I’ve tried to research the impact of fibroids on pregnancy and miscarriage, but information is very conflicting and I have not been able to find relieable detailed information. Do you feel that addressing a submucosal fibroid by “scraping it” through a hysteroscopic myectomy is effective? Is Lupron something that you recommend pursuing to attempt to shrink fibroids when trying to address fertility? If Lupron shots are used, do you need to delay attempting to get pregnant or doing a transfer for a specific period of time after the administration of the last Lupron shot? Do you think that the fibroid could be the cause of my miscarriages? Is there anything else that you think I should test to rule out?
I also recently read some information that suggested that women with shorter follicular phases and lighter menstrual bleeds also have increased incidence of miscarriage. My follicular phase typically is between 10 to 13 days and I have only been bleeding moderately to lightly for three to four days on average over the last couple of years. I also feel like my menstrual flow is lighter after my two D&Cs (one for the polypectomy and the other following my first miscarriage). Could this be negatively impacting my ability to carry a baby to term? Do you have any thoughts on this?
We were very hopeful for our pregnancy that happened naturally, but I am now very guarded with our prospects moving forward, even with IVF since I fear losing the pregnancy even if we have successful implantation.
I would be grateful for your input regarding our situation. Thank you in advance!
Needless to say, this sounds like an implantation dysfunction (anatomical and/or immunologic). Yes indeed, surface lesions encroaching upon, or protruding into the uterine cavity can cause failed implantation or early pregnancy loss. Importantly, some hysteroscopic surgeons settle for shaving fibroids to make the uterine caviy and lining smooth. In my opinion, unless the submucous fibroid is COMPLETELY removed (enucleated), this problem is NOT eliminated. It would be important to determine whether the entire fibroid was removed in your case.
The second issue is whether the immunologic testing performed to identify NK cell activation was adequately done. Please remember, the concentration of N K cells is irrelevant . Rather it is the NK cell activity (NKa) based upon the K-562 target cell test and/or endometrial TH1 cytokines that need to be assessed. Further more, there are no more than 4-6 Reproductive Immunology Reference Laboratories in the USA that can perform these tests adequately. And if, as I suspect might bed the case with you, you in fact do have NKa then the next step is to determined whether this is autoimmune or alloimmune in nature, as the treatment differs. Please do not ignore the possibility that the prior immune testing you did could have been inadequate.
Then there is the issue of endometrial thickness! This too needs to be considered. It should be >8mm at the point of the hCG trigger or at the time of progesterone therapy.
Finally, I strongly recommend Staggered IVF using an agonist/antagonist conversion protocol with Human Growth hormone ()HGH) and corticosteroid supplementation (seed below).
In my opinion, the protocol used for ovarian stimulation, against the backdrop of age, and ovarian reserve are the drivers of egg quality and egg quality is the most important factor affecting embryo “competency”.
Women who (regardless of age) have DOR have a reduced potential for IVF success. Much of this is due to the fact that such women tend to have increased production of LH biological activity which can result in excessive LH-induced ovarian male hormone (predominantly testosterone) production which in turn can have a deleterious effect on egg/embryo “competency”.
While it is presently not possible by any means, to reverse the effect of DOR, certain ovarian stimulation regimes, by promoting excessive LH production (e.g. short agonist/Lupron- “flare” protocols, clomiphene and Letrozole), can in my opinion, make matters worse. Similarly, the amount/dosage of certain fertility drugs that contain LH/hCG (e.g. Menopur) can have a negative effect on the development of the eggs of older women and those who have DOR and should be limited.I try to avoid using such protocols/regimes (especially) in women with DOR, favoring instead the use of the agonist/antagonist conversion protocol (A/ACP), a modified, long pituitary down-regulation regime, augmented by adding supplementary human growth hormone (HGH). I further recommend that such women be offered access to embryo banking of PGS (next generation gene sequencing/NGS)-selected normal blastocysts, the subsequent selective transfer of which by allowing them to capitalize on whatever residual ovarian reserve and egg quality might still exist and thereby “make hay while the sun still shines” could significantly enhance the opportunity to achieve a viable pregnancy.
Please visit my new Blog on this very site, https://www.drgeoffreysherivf.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
IVF Failure and Implantation Dysfunction:
•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!
•Endometrial Thickness, Uterine Pathology and Immunologic Factors
•Vaginally Administered Viagra is Often a Highly Effective Treatment to Help Thicken a Thin Uterine Lining
•Treating Out-of-State and Out-of-Country Patients at Sher-IVF in Las Vegas:
If you are interested in seeking my advice or 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 .
*FYI
The 4th edition of my newest 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.
Geoffrey Sher MD
Hi Dr Sher,
My husband and I share a partial DQ Alpha Gene, high NK cells and have not had any success using IVF and immune meds. We are now going to peruse a gestational surrogate. Can you please advise if the surrogate can have an immune reaction to our embryo’s?
Thank you.
If you have a DQa (p) match with your partner+ NKa, this could absolutely explain your issue. Treatment with 20% intralipid administered 10-14 days prior to ET and accompanying prednisone with single embryo transfer is what is needed. In my opinion, the transfer of >1 embryo at a time in such cases compromised outcome.
If you elect to use a surrogate, provided that she does NOT have NK cell activation (regardless of her DQa status) , she should be fine and the embryos would not be compromise in my opinion.
If you would like to discuss your case with me in more detail before going to surrogacy, please contact my assistant, Julie Dahan at 800-780-7437 or julied@sherivf.com to set up a Skype consultation.
Geoff Sher
Hi Dr. Sher, thank you for your response. I have tried 20% intrallipids with dexmethesone as well as IVIG and many other things, I have always transferred only 1 embryo at a time. This is why I am looking into a gestational surrogate. Would transferring 2 embryos into the surrogate be ok if she does not have any NK cell activation? Is the best way to test her for NK activity via biopsy or blood?