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.
Hi Dr Sher
I am 35 years old, my husband is 34. We have recently experienced our second IVF failure and am trying to better understand what might have gone wrong.
We have two naturally conceived children aged 4 and 2. We have been trying to conceive a third baby for 15 months, and have spent the last 5 months investigating and undertaking IVF (with ICSI) after my husband was diagnosed with poor morphology and high viscosity last summer. Note though that his sperm quality seems to have improved though and his last sample was said to have 4% morphology and look good. I have (bar some distruption around Ivf cycles) regular 30 day cycles bleeding for 4-5 days. The only other thing I think to mention by way of context is that I have been experiencing quite severe night sweating for the past 8 months or so before and during my period. I have had my thyroid tested and asked my RE about perimenopause and he said he saw no issues on either front after bloodwork.
With our first cycle, we had 12 eggs retrieved, 6 mature, 2 fertilised and transferred at 3 days. My period started 4 days before test day. I then got a positive test result but within 48 hours was told HCG was dropping and it was a biochemical pregnancy. With the second cycle, we had 12 eggs retrieved, 8 mature, 5 fertilised but only 2 survived to blastocyst stage and they were both transferred. Again I started bleeding 4 days before my test day.
My feeling is that the timing of my cycles has been wrong relative to the receptivenesss of my endometrium. My progesterone levels have been noted as high around the time of egg retrieval and transfer (190 the day before transfer, I can’t recall the other reading), which I expressed concern about but nothing changed in my protocol. I asked for progesterone to be tested after transfer and it was low, I think, at 36 3 days after transfer and 33 5 days after transfer. My RE increased me from 2 400mg cyclogest a day to 3 after the 36 reading. But a few days later bleeding started. For both cycles my night sweating has begun a few days after egg transfer, making me feel that my period is coming and progesterone levels are falling. I don’t know if this is the right thing to be focussed on or not and would be so grateful for your thoughts and perspective. I want to make sure I am asking the right questions and encouraging focus in the right direction.
Many thanks,
Amy
Many thanks,
Amy
Whenever a patient fails to achieve a viable pregnancy following embryo transfer (ET), the first question asked is why! Was it simply due to, bad luck?, How likely is the failure to recur in future attempts and what can be done differently, to avoid it happening next time?.
It is an indisputable fact that any IVF procedure is at least as likely to fail as it is to succeed. Thus when it comes to outcome, luck is an undeniable factor. Notwithstanding, it is incumbent upon the treating physician to carefully consider and address the causes of IVF failure before proceeding to another attempt:
1.Age: The chance of a woman under 35Y of age having a baby per embryo transfer is about 35-40%. From there it declines progressively to under 5% by the time she reaches her mid-forties. This is largely due to declining chromosomal integrity of the eggs with advancing age…”a wear and tear effect” on eggs that are in the ovaries from birth.
2.Embryo Quality/”competency (capable of propagating a viable pregnancy)”. As stated, the woman’s age plays a big role in determining egg/embryo quality/”competency”. This having been said, aside from age the protocol used for controlled ovarian stimulation (COS) is the next most important factor. It is especially important when it comes to older women, and women with diminished ovarian reserve (DOR) where it becomes essential to be aggressive, and to customize and individualize the ovarian stimulation protocol.
We used to believe that the uterine environment is more beneficial to embryo development than is the incubator/petri dish and that accordingly, the earlier on in development that embryos are transferred to the uterus, the better. To achieve this goal, we used to select embryos for transfer based upon their day two or microscopic appearance (“grade”). But we have since learned that the further an embryo has advanced in its development, the more likely it is to be “competent” and that embryos failing to reach the expanded blastocyst stage within 5-6 days of being fertilized are almost invariably “incompetent” and are unworthy of being transferred. Moreover, the introduction into clinical practice about a decade ago, (by Levent Keskintepe PhD and myself) of Preimplantation Genetic Sampling (PGS), which assesses for the presence of all the embryos chromosomes (complete chromosomal karyotyping), provides another tool by which to select the most “competent” embryos for transfer. This methodology has selective benefit when it comes to older women, women with DOR, cases of unexplained repeated IVF failure and women who experience recurrent pregnancy loss (RPL).
3.The number of the embryos transferred: Most patients believe that the more embryos transferred the greater the chance of success. To some extent this might be true, but if the problem lies with the use of a suboptimal COS protocol, transferring more embryos at a time won’t improve the chance of success. Nor will the transfer of a greater number of embryos solve an underlying embryo implantation dysfunction (anatomical molecular or immunologic).Moreover, the transfer of multiple embryos, should they implant, can and all too often does result in triplets or greater (high order multiples) which increases the incidence of maternal pregnancy-induced complications and of premature delivery with its serious risks to the newborn. It is for this reason that I rarely recommend the transfer of more than 2 embryos at a time and am moving in the direction of advising single embryo transfers …especially when it comes to transferring embryos derived through the fertilization of eggs from young women.
4.Implantation Dysfunction (ID): Implantation dysfunction is a very common (often overlooked) cause of “unexplained” IVF failure. This is especially the case in young ovulating women who have normal ovarian reserve and have fertile partners. Failure to identify, typify, and address such issues is, in my opinion, an unfortunate and relatively common cause of repeated IVF failure in such women. Common sense dictates that if ultrasound guided embryo transfer is performed competently and yet repeated IVF attempts fail to propagate a viable pregnancy, implantation dysfunction must be seriously considered. Yet ID is probably the most overlooked factor. The most common causes of implantation dysfunction are:
a.A“ thin uterine lining”
b.A uterus with surface lesions in the cavity (polyps, fibroids, scar tissue)
c.Immunologic implantation dysfunction (IID)
d.Endocrine/molecular endometrial receptivity issues
e.Ureaplasma Urealyticum (UU) Infection of cervical mucous and the endometrial lining of the uterus, can sometimes present as unexplained early pregnancy loss or unexplained failure following intrauterine insemination or IVF. The infection can also occur in the man, (prostatitis) and thus can go back and forth between partners, with sexual intercourse. This is the reason why both partners must be tested and if positive, should be treated contemporaneously.
Certain causes of infertility are repetitive and thus cannot readily be reversed. Examples include advanced age of the woman; severe male infertility; immunologic infertility associated with alloimmune implantation dysfunction (especially if it is a “complete DQ alpha genetic match between partners plus uterine natural killer cell activation (NKa).
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.
•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
ADDENDUM:
Sher-Fertility Solutions (SFS) will be officially launched in April 2019. Through SFS I will provide fertility consultations (via SKYPE) to an ever-growing number of patients (from >40 countries) with complex Reproductive Dysfunction (RD) who seek access to my input and guidance.
In the past, I have limited my consultations with patients from afar to those who expressed a willingness to travel to Las Vegas for treatment by me. But now with the “birth” of SFS, all this is about to change. With one notable exception I will, as of April, 2019, no longer be conducting and performing hands-on IVF treatments. Rather, I will focus on providing SKYPE consultations and guidance to as many patients as possible. The one important exception will apply to approximately 1,000 existing patients who, following IVF previously performed by me, have remaining eggs or embryos stored (cryopreserved) at SIRM-LV and wish for me to perform their Frozen Embryo Transfers (FETs). I have agreed to accommodate such patients…..but only through August, 2019.
Patients will have ready access online, to SFS: by going to http://www.SherIVF.com; by phone (1-800-780-7437 or 702-533-2691) and via email (sher@sherivf.com or concierge@sherIVF.com). A onetime fee of $400.00, will provide enrollees with access to: a full review of all their medical records (+ assistance in requisitioning additional records, as needed); a comprehensive initial 1 hour, SKYPE consultation with me; additional SKYPE consultations (as might be required); a written medical report (which will include a recommended plan of action) that you can share with a Physician(s) of choice. I would, subject to your approval and a request by such Physician(s), also be willing to discuss your case with him/her/them. I will in due course post on my website, a list of Fertility Physicians in key locations all over the United States and abroad, whom I endorse and to whom I would be willing to direct SFS patients for subsequent treatment.
I have good news for those of you who are interested in traveling to Las Vegas for IVF. Dr Russel Foulk, Medical Director of SIRM-LV has expressed a willingness to be receptive to, treatment plans that I recommend for SFS patients Moreover, Dr Foulk has graciously agreed to interact with me during such treatments. I highly recommend Dr Foulk to those of you who, following consultation with me, wish to have me remain involved in the implementation of your treatment. This having been said, the final say in any management decision is always up to the treating physician.
It is both my objective and commitment to serve as a resource to SFS patients on complex RD issues such as: Unexplained IVF failure; Recurrent Pregnancy loss (RPL); Immunologic Implantation Dysfunction-IID; Genetic/chromosomal issues; effects of Diminished Ovarian Reserve (DOR) and advancing age on reproductive performance, etc.
I hope to ultimately expand the National and International reach of SFS, through my website (www.sherIVF.com) , through online webinars as well as Town hall- type consumer-based seminars, workshops and through social media. At the same time I will continue blogging on my website and doing bi-weekly Live-feed Facebook presentations (at “Dr Geoffrey Sher”) on a variety of subjects and topical issues.
For me this is a very exciting venture. Please become part of the SFS family and help spread the word!
I was very recently greatly honored in receiving an award by the prestigious; International Association of Top Professionals (IAOTP). For more information, go to the press release on my website, http://www.sherIVF.com
Hello Dr. Sher
I am 25 yrs old with PCO and history of pelvic TB. Tubes are open but had no pregnancy in the past. I had FET on 02/05/2019 with two blastocysts. Beta hcg on 02/15/2019 is 43.4mIU/ml. Is this a good number? Does it look positive?
Very encouraging!
Good luck!
Geoff Sher
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ADDENDUM
Sher-Fertility Solutions (SFS) will be officially launched in April 2019. Through SFS I will provide fertility consultations (via SKYPE) to an ever-growing number of patients (from >40 countries) with complex Reproductive Dysfunction (RD) who seek access to my input and guidance.
In the past, I have limited my consultations with patients from afar to those who expressed a willingness to travel to Las Vegas for treatment by me. But now with the “birth” of SFS, all this is about to change. With one notable exception I will, as of April, 2019, no longer be conducting and performing hands-on IVF treatments. Rather, I will focus on providing SKYPE consultations and guidance to as many patients as possible. The one important exception will apply to approximately 1,000 existing patients who, following IVF previously performed by me, have remaining eggs or embryos stored (cryopreserved) at SIRM-LV and wish for me to perform their Frozen Embryo Transfers (FETs). I have agreed to accommodate such patients…..but only through August, 2019.
Patients will have ready access online, to SFS: by going to http://www.SherIVF.com; by phone (1-800-780-7437 or 702-533-2691) and via email (sher@sherivf.com or concierge@sherIVF.com). A onetime fee of $400.00, will provide enrollees with access to: a full review of all their medical records (+ assistance in requisitioning additional records, as needed); a comprehensive initial 1 hour, SKYPE consultation with me; additional SKYPE consultations (as might be required); a written medical report (which will include a recommended plan of action) that you can share with a Physician(s) of choice. I would, subject to your approval and a request by such Physician(s), also be willing to discuss your case with him/her/them. I will in due course post on my website, a list of Fertility Physicians in key locations all over the United States and abroad, whom I endorse and to whom I would be willing to direct SFS patients for subsequent treatment.
I have good news for those of you who are interested in traveling to Las Vegas for IVF. Dr Russel Foulk, Medical Director of SIRM-LV has expressed a willingness to be receptive to, treatment plans that I recommend for SFS patients Moreover, Dr Foulk has graciously agreed to interact with me during such treatments. I highly recommend Dr Foulk to those of you who, following consultation with me, wish to have me remain involved in the implementation of your treatment. This having been said, the final say in any management decision is always up to the treating physician.
It is both my objective and commitment to serve as a resource to SFS patients on complex RD issues such as: Unexplained IVF failure; Recurrent Pregnancy loss (RPL); Immunologic Implantation Dysfunction-IID; Genetic/chromosomal issues; effects of Diminished Ovarian Reserve (DOR) and advancing age on reproductive performance, etc.
I hope to ultimately expand the National and International reach of SFS, through my website (www.sherIVF.com) , through online webinars as well as Town hall- type consumer-based seminars, workshops and through social media. At the same time I will continue blogging on my website and doing bi-weekly Live-feed Facebook presentations (at “Dr Geoffrey Sher”) on a variety of subjects and topical issues.
For me this is a very exciting venture. Please become part of the SFS family and help spread the word!
I was very recently greatly honored in receiving an award by the prestigious; International Association of Top Professionals (IAOTP). For more information, go to the press release on my website, http://www.sherIVF.com .
.
I have a question about your blog when you discuss Asherman’s syndrome. You say “The condition often results in fusion/adhesion of the opposing endometrial surfaces, but can also simply destroy the basal layer of endometrium without resulting in adhesions (non-adhesive Asherman’s).” I recently have a thinner lining after a surgery, but no scarring was detected on the hysteroscopy. Is this what you mean by non-adhesive? Thank you for your help. I am trying to find more information on this type of condition, “non-adhesive Asherman’s,” but can’t find any information.
In addition, I came across this article: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2582129/
“A possible explanation to this observation might be the existence of a spectrum of post curettage endometrial injuries ranging from a thin and unresponsive (but otherwise normal) endometrium at one end, to Asherman’s syndrome on the other. ” I was wondering if this is the type of non-adhesive Asherman’s you were describing. thanks again!
It is uncommon, but possible that sharp curettage done over zealously, can cause permanent damage to the basal endometrium. But what I was referring to in my blog ids that post-pregnancy endometritis can permeate and damage the basal (germinal) endometrium without there necessarily being adhesions. A hysteroscopy might find no evidence of scarring in such cases which can equally damage endometrial response (proliferation) to estrogen.
Geoff Sher
Hi Dr Sher
I’ve been following your work for a while and find it so valuable, thank you! I would really appreciate your thoughts on my fertility journey – I am almost 40 and my partner is 52, he has children from previous relationships but unfortunately I have miscarried twice and have no children.
We have undergone IVF 3 times and had 1 FET –
1st cycle 2017 – my stims dose was increased from 375 to 400iu Bemfola after initial scans, I had about 8 follicles and a large cyst formed on one ovary. It was noted that there were adhesions on this ovary too. I had only 2 eggs collected, bother fertilised and i had one blastocyst transferred on Day 5 but got a negative test
2nd cycle August 2017 – 1 grade AB stage 5 blastocyst transferred, I initially tested negative on test day but my period didn’t arrive and i got a positive test a few days later. I had a scan at 6 weeks and all was well but I miscarried at about 10 weeks, all tests came back normal
3rd Cycle Feb 2018. I started on 800mcg Synarel spray from Day 21 the continued this for 4 weeks. I then continued to take it along with 450iu Bemfola for 13 days. Scans showed 4 good follicles and got 3 eggs collected, 2 were transferred and 1 frozen. I got a positive test but miscarried at 12 weeks 5 days. All samples from the miscarriage were normal.
FET cycle Dec 2018 – I had my remaining embryo transferred but received a negative test at the end of the two week wait.
All hormone tests and investigations have come back normal and my partners tests are all normal too however after over 10years together we have no conceived naturally.
We are cautious of continuing with further IVF – what would your thoughts be? Should we have any tests or scans done before going forward with anything? What do you think our chances would be? I appreciate any advice you have for us. I am based in the UK and coming to you for treatment wouldn’t be possible at this time.
Many thanks
D
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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.SherIVF.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
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ADDENDUM:
Sher-Fertility Solutions (SFS) will be officially launched in April 2019. Through SFS I will provide fertility consultations (via SKYPE) to an ever-growing number of patients (from >40 countries) with complex Reproductive Dysfunction (RD) who seek access to my input and guidance.
In the past, I have limited my consultations with patients from afar to those who expressed a willingness to travel to Las Vegas for treatment by me. But now with the “birth” of SFS, all this is about to change. With one notable exception I will, as of April, 2019, no longer be conducting and performing hands-on IVF treatments. Rather, I will focus on providing SKYPE consultations and guidance to as many patients as possible. The one important exception will apply to approximately 1,000 existing patients who, following IVF previously performed by me, have remaining eggs or embryos stored (cryopreserved) at SIRM-LV and wish for me to perform their Frozen Embryo Transfers (FETs). I have agreed to accommodate such patients…..but only through August, 2019.
Patients will have ready access online, to SFS: by going to http://www.SherIVF.com; by phone (1-800-780-7437 or 702-533-2691) and via email (sher@sherivf.com or concierge@sherIVF.com). A onetime fee of $400.00, will provide enrollees with access to: a full review of all their medical records (+ assistance in requisitioning additional records, as needed); a comprehensive initial 1 hour, SKYPE consultation with me; additional SKYPE consultations (as might be required); a written medical report (which will include a recommended plan of action) that you can share with a Physician(s) of choice. I would, subject to your approval and a request by such Physician(s), also be willing to discuss your case with him/her/them. I will in due course post on my website, a list of Fertility Physicians in key locations all over the United States and abroad, whom I endorse and to whom I would be willing to direct SFS patients for subsequent treatment.
I have good news for those of you who are interested in traveling to Las Vegas for IVF. Dr Russel Foulk, Medical Director of SIRM-LV has expressed a willingness to be receptive to, treatment plans that I recommend for SFS patients Moreover, Dr Foulk has graciously agreed to interact with me during such treatments. I highly recommend Dr Foulk to those of you who, following consultation with me, wish to have me remain involved in the implementation of your treatment. This having been said, the final say in any management decision is always up to the treating physician.
It is both my objective and commitment to serve as a resource to SFS patients on complex RD issues such as: Unexplained IVF failure; Recurrent Pregnancy loss (RPL); Immunologic Implantation Dysfunction-IID; Genetic/chromosomal issues; effects of Diminished Ovarian Reserve (DOR) and advancing age on reproductive performance, etc.
I hope to ultimately expand the National and International reach of SFS, through my website (www.sherIVF.com) , through online webinars as well as Town hall- type consumer-based seminars, workshops and through social media. At the same time I will continue blogging on my website and doing bi-weekly Live-feed Facebook presentations (at “Dr Geoffrey Sher”) on a variety of subjects and topical issues.
For me this is a very exciting venture. Please become part of the SFS family and help spread the word!
I was very recently greatly honored in receiving an award by the prestigious; International Association of Top Professionals (IAOTP). For more information, go to the press release on my website, http://www.sherIVF.com .
I am 33 years old. Last year I had IVF. I sent 7 blastocysts for PGS testing and 3 came back normal. They transferred one, which resulted in my beautiful baby girl. Last week I went in for my second FET and was told 1 of the 2 remaining blastocysts did not survive thaw and the 3rd and final blastocyst was implanted. I’m wondering how unusual it is for that blast to not have survived thaw. I thought vitrification yielded a 90% successful thaw. Am I just unlucky?
It can and does sometimes happen, unfortunately!
Good luck!
Geoff Sher
_______________________________________________________________________________
ADDENDUM:
Sher-Fertility Solutions (SFS) will be officially launched in April 2019. Through SFS I will provide fertility consultations (via SKYPE) to an ever-growing number of patients (from >40 countries) with complex Reproductive Dysfunction (RD) who seek access to my input and guidance.
In the past, I have limited my consultations with patients from afar to those who expressed a willingness to travel to Las Vegas for treatment by me. But now with the “birth” of SFS, all this is about to change. With one notable exception I will, as of April, 2019, no longer be conducting and performing hands-on IVF treatments. Rather, I will focus on providing SKYPE consultations and guidance to as many patients as possible. The one important exception will apply to approximately 1,000 existing patients who, following IVF previously performed by me, have remaining eggs or embryos stored (cryopreserved) at SIRM-LV and wish for me to perform their Frozen Embryo Transfers (FETs). I have agreed to accommodate such patients…..but only through August, 2019.
Patients will have ready access online, to SFS: by going to http://www.SherIVF.com; by phone (1-800-780-7437 or 702-533-2691) and via email (sher@sherivf.com or concierge@sherIVF.com). A onetime fee of $400.00, will provide enrollees with access to: a full review of all their medical records (+ assistance in requisitioning additional records, as needed); a comprehensive initial 1 hour, SKYPE consultation with me; additional SKYPE consultations (as might be required); a written medical report (which will include a recommended plan of action) that you can share with a Physician(s) of choice. I would, subject to your approval and a request by such Physician(s), also be willing to discuss your case with him/her/them. I will in due course post on my website, a list of Fertility Physicians in key locations all over the United States and abroad, whom I endorse and to whom I would be willing to direct SFS patients for subsequent treatment.
I have good news for those of you who are interested in traveling to Las Vegas for IVF. Dr Russel Foulk, Medical Director of SIRM-LV has expressed a willingness to be receptive to, treatment plans that I recommend for SFS patients Moreover, Dr Foulk has graciously agreed to interact with me during such treatments. I highly recommend Dr Foulk to those of you who, following consultation with me, wish to have me remain involved in the implementation of your treatment. This having been said, the final say in any management decision is always up to the treating physician.
It is both my objective and commitment to serve as a resource to SFS patients on complex RD issues such as: Unexplained IVF failure; Recurrent Pregnancy loss (RPL); Immunologic Implantation Dysfunction-IID; Genetic/chromosomal issues; effects of Diminished Ovarian Reserve (DOR) and advancing age on reproductive performance, etc.
I hope to ultimately expand the National and International reach of SFS, through my website (www.sherIVF.com) , through online webinars as well as Town hall- type consumer-based seminars, workshops and through social media. At the same time I will continue blogging on my website and doing bi-weekly Live-feed Facebook presentations (at “Dr Geoffrey Sher”) on a variety of subjects and topical issues.
For me this is a very exciting venture. Please become part of the SFS family and help spread the word!
I was very recently greatly honored in receiving an award by the prestigious; International Association of Top Professionals (IAOTP). For more information, go to the press release on my website, http://www.sherIVF.com .