19,771 Comments

1. Deb on May 17, 2018 at 9:46 pm

   Hi Dr. Sher. Would you transfer a trisomy 22 6 day blastocyst? I read that there can be a placental variant of trisomy 22 where the fetus is normal or slightly growth restricted. Theoretically, since the PGS sample is taken from the trophoblast layer and not the inner cell mass, could the trisomy be confined to the placenta? If so, how would you determine the difference? Thank you for your response.

   • Dr. Geoffrey Sher on May 18, 2018 at 12:22 am

     I doubt it is confined to the placenta!

     Geoff Sher

2. Denise on May 17, 2018 at 7:29 pm

   Hi Dr. Sher,

   For my upcoming FET, my doctor wants my uterine lining to be trilaminar and measure between 6.5 to 12mm. (I think you prefer >8mm). Within this range, is there a “best” measurement that has the highest implantation rate?

   Thankfully I do not have a problem with growing my lining, but my doctor did my last FET at 7mm. The PGS embryo implanted but had a small gestational sac and slight detachment (small subchorionic hemmorage). Would having a thicker lining prior to transfer help improve the gestational sac size or detachment issue?

   Thanks!

   • Dr. Geoffrey Sher on May 18, 2018 at 12:23 am

     It was as far back as 1989, when I first published a study that examined the correlation between the thickness of a woman’s uterine lining (the endometrium), and the subsequent successful implantation of embryos in IVF patients. This study revealed that when the uterine lining measured <8mm in thickness by the day of the “hCG trigger” (in fresh IVF cycles), or at the time of initiating progesterone therapy (in embryo recipient cycles, e.g. frozen embryo transfers-FET, egg donation-IVF etc.) , pregnancy and birth rates were substantially improved. Currently, it is my opinion, that an ideal estrogen-promoted endometrial lining should ideally measure at least 9mm in thickness and that an endometrial lining measuring 8-9mm is “intermediate”. An estrogenic lining of <8mm is in most cases unlikely to yield a viable pregnancy.

     A “poor” uterine lining is usually the result of the innermost layer of endometrium (the basal or germinal endometrium from which endometrium grows) ) not being able to respond to estrogen by propagating an outer, “functional” layer thick enough to support optimal embryo implantation and development of a healthy placenta (placentation). The “functional” layer ultimately comprises 2/3 of the full endometrial thickness and is the layer that sheds with menstruation in the event that no pregnancy occurs.

     The main causes of a “poor” uterine lining are:

     1.Damage to the basal endometrium as a result of:
     a.Inflammation of the endometrium (endometritis) most commonly resulting from infected products left over following abortion, miscarriage or birth
     b.Surgical trauma due to traumatic uterine scraping, (i.e. due to an over-aggressive D & C)
     2.Insensitivity of the basal endometrium to estrogen due to:
     a.Prolonged , over-use/misuse of clomiphene citrate
     b.Prenatal exposure to diethylstilbestrol (DES). This is a drug that was given to pregnant women in the 1960’s to help prevent miscarriage
     3.Over-exposure of the uterine lining to ovarian male hormones (mainly testosterone): Older women, women with diminished ovarian reserve (poor responders) and women with polycystic ovarian syndrome -PCOS tend to have raised LH biological activity.. This causes the connective tissue in the ovary (stroma/theca) to overproduce testosterone. The effect can be further exaggerated when certain methods for ovarian stimulation such as agonist (Lupron/Buserelin) “flare” protocols and high dosages of menotropins such as Menopur are used in such cases.
     4.Reduced blood flow to the basal endometrium:
     Examples include;
     a.Multiple uterine fibroids - especially when these are present under the endometrium (submucosal)
     b.Uterine adenomyosis (excessive, abnormal invasion of the uterine muscle by endometrial glands).

     “The Viagra Connection”

     Eighteen years ago years ago, after reporting on the benefit of vaginal Sildenafil (Viagra) for to women who had implantation dysfunction due to thin endometrial linings I was proud to announce the birth of the world’s first “Viagra baby.” Since the introduction of this form of treatment, thousands of women with thin uterine linings have been reported treated and many have gone on to have babies after repeated prior IVF failure.

     For those of you who aren’t familiar with the use of Viagra in IVF, allow me to provide some context. It was in the 90’s that Sildenafil (brand named Viagra) started gaining popularity as a treatment for erectile dysfunction. The mechanism by which it acted was through increasing penile blood flow through increasing nitric oxide activity. This prompted me to investigate whether Viagra administered vaginally, might similarly improve uterine blood flow and in the process cause more estrogen to be delivered to the basal endometrium and thereby increase endometrial thickening. We found that when Viagra was administered vaginally it did just that! However oral administration was without any significant benefit in this regard. We enlisted the services of a compound pharmacy to produce vaginal Viagra suppositories. Initially, four (4) women with chronic histories of poor endometrial development and failure to conceive following several advanced fertility treatments were evaluated for a period of 4-6 weeks and then underwent IVF with concomitant Viagra therapy. Viagra suppositories were administered four times daily for 8-11 days and were discontinued 5-7 days prior to embryo transfer in all cases.

     Our findings clearly demonstrated that vaginal Viagra produced a rapid and profound improvement in uterine blood flow and that was followed by enhanced endometrial development in all four cases. Three (3) of the four women subsequently conceived. I expanded the trial in 2002 and became the first to report on the administration of vaginal Viagra to 105 women with repeated IVF failure due to persistently thin endometrial linings. All of the women had experienced at least two (2) prior IVF failures attributed to intractably thin uterine linings. About 70% of these women responded to treatment with Viagra suppositories with a marked improvement in endometrial thickness. Forty five percent (45%) achieved live births following a single cycle of IVF treatment with Viagra The miscarriage rate was 9%. None of the women who had failed to show an improvement in endometrial thickness following Viagra treatment achieved viable pregnancies.

     Following vaginal administration, Viagra is rapidly absorbed and quickly reaches the uterine blood system in high concentrations. Thereupon it dilutes out as it is absorbed into the systemic circulation. This probably explains why treatment is virtually devoid of systemic side effects

     It is important to recognize that Viagra will NOT be effective in improving endometrial thickness in all cases. In fact, about 30%-40% of women treated fail to show any improvement. This is because in certain cases of thin uterine linings, the basal endometrium will have been permanently damaged and left unresponsive to estrogen. This happens in cases of severe endometrial damage due mainly to post-pregnancy endometritis (inflammation), chronic granulomatous inflammation due to uterine tuberculosis (hardly ever seen in the United States) and following extensive surgical injury to the basal endometrium (as sometimes occurs following over-zealous D&C’s).

     Combining vaginal Viagra Therapy with oral Terbutaline;
     In my practice I sometimes recommend combining Viagra administration with 5mg of oral terbutaline. The Viagra relaxes the muscle walls of uterine spiral arteries that feed the basal (germinal) layer of the endometrium while Terbutaline, relaxes the uterine muscle through which these spiral arteries pass. The combination of these two medications interacts synergistically to maximally enhance blood flow through the uterus, thereby improving estrogen delivery to the endometrial lining. The only drawback in using Terbutaline is that some women experience agitation, tremors and palpitations. In such cases the terbutaline should be discontinued. Terbutaline should also not be used women who have cardiac disease or in those who have an irregular heartbeat.
     About 75% of women with thin uterine linings see a positive response to treatment within 2-3 days. The ones that do not respond well to this treatment are those who have severely damaged inner (basal/germinal) endometrial linings, such that no improvement in uterine blood flow can coax an improved response. Such cases are most commonly the result of prior pregnancy-related endometrial inflammation (endometritis) that sometimes occurs post abortally or following infected vaginal and/or cesarean delivery.
     Viagra therapy has proven to be a god send to thousands of woman who because of a thin uterine lining would otherwise never have been able to successfully complete the journey “from infertility to family”.

     To be effective, Viagra must be administered vaginally. It is NOT effective when taken orally. We prescribe 20mg vaginal suppositories to be inserted four times per day. Treatment is commenced soon after menstruation ceases and is continued until the day of the “hCG trigger.” While ideally the treatment should be sustained throughout the first half of the cycle, most women will respond within 48-72 hours. For this reason, Viagra can be used to “rescue” a poor lining after the cycle has already started, provided that there is enough time remaining prior to ovulation, egg retrieval or progesterone administration.

     Geoff Sher

3. Niamh on May 17, 2018 at 10:43 am

   I recently had an unsuccessful ivf cycle. I had one NGS embryo (with no abnormalities), I did an ERA which said that I was on the cusp of being post-receptive so we reduced one dose of crinone gel (by 12 hours). I did have raised TH1 and TH2 cytokines which was brought back into normal range using humira and misema. Everything looked perfect. My consultant felt assured that I would have a 95 per cent chance of becoming pregnant but unfortunately I didnt. I had a review appointment to try to figure out why the cycle was unsuccessful. My consultant feels that its an uncommon / rare auto immune problem. I am wondering what you might think it might be. I am 43 years in 3 months time so my time is running out in terms of getting another healthy embryo. I don’t think its implantation problems as I have 2 healthy children. I did have pink crinone gel discharge very early on post transfer so I would imagine I started to shed the lining of the uterus very early on. Thanking you.

   • Dr. Geoffrey Sher on May 17, 2018 at 6:46 pm

     Few people are born with an underlying uterine NK cell issue. Your uterine cytokine test suggests that you do have an immunologic implantation dysfunction linked to NK cell activation and in my opinion, Humira is not the ideal treatment…even if it regulated uterine cytokines. First I think you should have a blood K-562 test (I recommend Reprosource in Boston, MA). It is in my oppinion a much more reliable indicator of NKa. If this is the problem the next step is to differentiate between an autoimmune and alloimmune cause because treatment would differ. If treatment is used, my suggestion is Intralipid + steroids, starting 10-14 days prior to ET.

     Unless tests for immunologic implantation dysfunction (IID) are performed correctly and conducted by a one of the few reliable reproductive immunology reference laboratory in the United States, treatment will likely be unsuccessful. . In this regard it is most important that the right tests be ordered and that these be performed by a competent laboratory. There are in my opinion only a handful of reliable Reproductive Immunology Laboratories in the world and most are in the U.S.A. Also, it is my opinion that far too often, testing is inappropriate with the many redundant and incorrect tests being requested from and conducted by suboptimal laboratories. Finally for treatment to have the best chance of being successful, it is vital that the underlying type of IID (autoimmune IID versus alloimmune) be identified correctly and that the type, dosage, concentration and timing of treatments be carefully devised and implemented.
     Who Should Undergo IID testing?
     When it comes to who should be evaluated, the following conditions should in always raise a suspicion of an underlying IID, and trigger prompt testing:
     •A diagnosis of endometriosis or the existence of symptoms suggestive of endometriosis (heavy/painful menstruation and pain with ovulation or with deep penetration during intercourse) I would however emphasize that a definitive diagnosis of endometriosis requires visualization of the lesions at laparoscopy or laparotomy)
     •A personal or family history of autoimmune disease such as hyper/hypothyroidism (as those with elevated or depressed TSH blood levels, regardless of thyroid hormonal dysfunction), Lupus erythematosus, Rheumatoid arthritis, dermatomyositis, scleroderma etc.)
     •“Unexplained” infertility
     •Recurrent pregnancy loss (RPL)
     •A history of having miscarried a conceptus that, upon testing of products of conception, was found to have a normal numerical chromosomal configuration (euploid).
     •Unexplained IVF failure
     • “Unexplained” intrauterine growth retardation due to placental insufficiency or late pregnancy loss of a chromosomally normal baby
     What Parameters should be tested?
     In my opinion, too many Reproductive Immunologists unnecessarily unload a barrage of costly IID tests on unsuspecting patients. In most cases the initial test should be for NK cell activation, and only if this is positive, is it necessary to expand the testing.
     The parameters that require measurement include:
     oFor Autoimmune Implantation Dysfunction: Autoimmune implantation dysfunction, most commonly presents with presumed “infertility” due to such early pregnancy losses that the woman did not even know she was pregnant in the first place. Sometimes there as an early miscarriage. Tests required are: a) blood levels of all IgA, IgG and IgM-related antiphospholipid antibodies (APA’s) directed against six or seven specific phospholipids, b) both antithyroid antibodies (antithyroid and antimicrosomal antibodies), c) a comprehensive reproductive immunophenotype (RIP) and, c) most importantly, assessment of Natural Killer (NK) cell activity (rather than concentration) by measuring by their killing, using the K-562 target cell test and/or uterine cytokine measurement. As far as the ideal environment for performing such tests, it is important to recognize that currently there are only about 5 or 6, Reproductive Immunology Reference Laboratories in the U.S capable of reliably analyzing the required elements with a sufficient degree of sensitivity and specificity (in my opinion).
     oFor Alloimmune implantation Dysfunction: While alloimmune Implantation usually presents with a history of unexplained (usually repeated) miscarriages or secondary infertility (where the woman conceived initially and thereupon was either unable to conceive started having repeated miscarriages it can also present as “presumed” primary infertility. Alloimmune dysfunction is diagnosed by testing the blood of both the male and female partners for matching DQ alpha genes and NK/CTL activation. It is important to note that any DQ alpha match (partial or complete) will only result in IID when there is concomitant NK/CTL activation (see elsewhere on this blog).
     How should results be interpreted?
     Central to making a diagnosis of an immunologic implantation dysfunction is the appropriate interpretation of natural killer cell activity (NKa) .In this regard, one of the commonest and most serious errors, is to regard the blood concentration of natural killer cells as being significant. Rather it is the activity (toxicity) of NK cells that matters as mentioned. Then there is the interpretation of reported results. The most important consideration is the percentage of target cells “killed” in the “native state”. In most cases a level of >10% killing should be regarded with suspicion and >12% overtly abnormal. In my opinion, trying to interpret the effect of adding IVIG or Intralipid to the sample in order assess whether and to what degree the use of these products would have a therapeutic benefit is seriously flawed and of little benefit. Clinically relevant NK cell deactivation can only be significantly effected in vivo and takes more than a week following infusion to occur. Thus what happens in the laboratory by adding these products to the sample prior to K-562 target cell testing is in my opinion likely irrelevant.
     There exists a pervasive but blatant misconception on the part of many, that the addition of Intralipid (IL) /immunoglobulin-G IVIG) can have an immediate down-regulatory effect on NK cell activity. This has established a demand that Reproductive Immunology Reference Laboratories report on NK cell activity before and following exposure to IVIG and/or IL. However, the fact is that activated “functional” NK cells (NKa) cannot be deactivated in the laboratory. Effective down-regulation of activated NK cells can only be adequately accomplished if their activated “progenitor/parental” NK cells are first down-regulated. Thereupon once these down-regulated “precursor” NK cells are exposed to progesterone, they will begin spawning normal and functional NK cells, which takes about 10-14 days. It follows that to assess for a therapeutic response to IVIG/IL therapy would require that the patient first be treated (10-14 days prior to embryo transfer) and thereupon, about 2 weeks later, be retested. While at 1st glance this might seem to be a reasonable approach, in reality it would be of little clinical benefit because even if blood were to be drawn 10 -14 days after IL/IVIG treatment it would require an additional 10 days to receive results from the laboratory, by which time it would be far too late to be of practical advantage.
     Neither IVIG nor IL is capable of significantly suppressing already activated “functional NK cells”. For this to happen, the IL/IVIG would have to down-regulate progenitor (parent) NK cell” activity. Thus, it should be infused 10-14 several prior to ovulation or progesterone administration so that the down-regulated “progenitor/precursor” NK cells” can propagate a sufficient number of normally regulated “functional NK cell” to be present at the implantation site 7 days later. In addition, to be effective, IL/IVIG therapy needs to be combined with steroid (dexamethasone/prednisone/prednisolone) therapy to down-regulates (often) concomitantly activated T-cells.

     The older a woman becomes, the more likely it is that her eggs will be chromosomally/genetically “incompetent” (not have the potential upon being fertilized and transferred, to result in a viable pregnancy). That is why, the likelihood of failure to conceive, miscarrying and of giving birth to a chromosomally defective child (e.g. with Down Syndrome) increases with the woman’s advancing age. In addition, as women age beyond 35Y there is commonly a progressive diminution in the number of eggs left in the ovaries, i.e. diminished ovarian reserve (DOR). So it is that older women as well as those 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 age-related effect on the woman’s “biological clock, certain ovarian stimulation regimes, by promoting excessive LH production (e.g. short agonist/Lupron- “flare” protocols, clomiphene and Letrozole), can 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 older women and those 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 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

     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.
     •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!

     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

     PS: Your age also makes it important to use a very inmdividualized protocol for ovarian stimulation and to do PGS on all blastocysts for selective FET.

4. Owen on May 17, 2018 at 2:07 am

   I am a 43-year-old woman, have one 12-year-old son who is healthy and delivered by cesarean birth 12 years ago. Now I am pregnant with twins for 10 weeks after IVF with donor egg. Could you please answer me a few of questions?
   1. Do I need to reduce one fetal? For my Scar uterus, selective fetal reduction is the better chioce?
   2. Do I need do Chorionic Villus Sampling (CVS) before selective fetal reduction? Is CVS needed to be done for one or both Embryo before selective fetal reduction?
   3. What is the probability of fetal DNA abnormality if I do not do CVS?
   4. What is the probability of miscarriage caused by CVS?
   I am looking forward and thank you very much for your answer!

   • Dr. Geoffrey Sher on May 17, 2018 at 2:24 am

     1. Do I need to reduce one fetal? For my Scar uterus, selective fetal reduction is the better choice?

     A: Barring unusual circumstances, I would advise against doing so!

     2. Do I need do Chorionic Villus Sampling (CVS) before selective fetal reduction? Is CVS needed to be done for one or both Embryo before selective fetal reduction?

     A: Probably so!

     3. What is the probability of fetal DNA abnormality if I do not do CVS?

     A: About !:80

     4. What is the probability of miscarriage caused by CVS?

     A: Very low if done by an expert.

     Good luck and G-d bless!

     Geoff Sher

5. Brandy on May 17, 2018 at 1:27 am

   My daughter wants to give me one of her eggs so that me and my husband can have a baby. How much would it cost us if the eggs are free?

   • Dr. Geoffrey Sher on May 17, 2018 at 2:22 am

     Roughly the same as a regular IVF. Please call Amanda Wells at 702-892-9696 (Office Manager) and ask her!

     Geoff Sher