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 recently turned 30 last month, my husband 29. No significant PMH. Our story is as follows:
May of 2019: found out I was pregnant (after a missed period) on the first cycle we attempted to conceive. At about 6 weeks, I had a one time episode of bright red bleeding. An US x2 a week apart could not detect anything intrauterine, though a mass by my left ovary was seen on both scans, questionable for ectopic. I was never really in any pain aside from a short 24 hour stint of intermittent and sporadic discomfort prior to the bleeding. I’d describe it as a one time instant/sharp quick pain followed by intermittent duller/achier pains, hard to say if it was lateralized to the left in hindsight, but again, I didn’t make much of it at the time; it didn’t “take my breath away” or necessarily cause me concern. I just laid down and thought hmm weird, and again, it was transient, only happened 1-2 times over the 24 hours, and totally went away. But anyway, HCG was trended and was rising, though abnormally slow (from 700 to 900 to 1100 to 1200 q48h apart). I received methotrexate on 6/5 and my HCG returned to 0 on 6/24. Was told to wait for one normal cycle before attempting again.
Before trying again, I became diligent about tracking my cycles using ovulation predictor kits, tracking BBT, etc. I pinpointed ovulation on 8/8 (cycle day 20) though got my period right on time as expected 12 days later on 8/20 (with spotting occurring approx 2-3 days prior on cycle day 29), so stopped taking pregnancy tests when my period officially arrived. Little did I know I actually conceived on 8/8, and the way I found out was because my next round of ovulation tests appeared dark every day I tested. I remember reading that OPKs cannot differentiate between LH and HCG, and sure enough, my pregnancy test was unequivocally positive on 9/1. Obviously I was concerned, as I just had what seemed like a normal period (seemed like a totally normal period, maybe in hindsight a little lighter, but nothing I appreciated in the moment). HCG and progesterone on 9/3 were 90 and .88, respectively. I was instructed to start taking progesterone, and it did rise to 16.68 in a week. Again, HCG trend q48h was as follows starting on 9/3: 90, 186, 351, 567, 866, then a week later 1122, then 1030 48h later.. and eventually dropping to 0 over what felt like an eternity on 11/15. No interventions were required, and no imaging was performed. I was told by my OB that I drew two unlucky straws, but the third time it was likely to succeed. He told me he could do a uterine biopsy to look for villi if I was really going to lose sleep over whether or not this pregnancy implanted in the uterus or not. I asked about an HSG, to which he said no, because an HSG would only look at gross anatomical structures, and fail to show us if anything is happening at the microscopic level. Told me to essentially try again and hope for the best.
Which brings me to now. I pinpointed ovulation on 12/5 (cycle day 20), tracked BBT, and got my first faintly positive test 11 days past ovulation (12/16). However, this the day I also got my period… FYI, I also did start spotting on cycle day 29 again (12/14). So these periods are acting like normal periods for me, lasting approximately 5 days, normal in color and volume. My first HCG on 12/18 was 16, with a progesterone of 7.44, and repeat 48 hours later on 12/20 HCG dropped to 15, progesterone was 5.49 (I was still bleeding from my “period” at this time). Well the bleeding has totally stopped now, and I have been trending my pregnancy test line progression, which does seem to appear like its slowly darkening. I’m just worried that my HCG will slowly start rising now, and that I’m about to repeat the 3 month saga I just went through last time. I have not heard back from my OB yet following my last lab draws, though I imagine we will just continue to trend HCG until either it falls on its own or an intervention is required…
To give you some background info that may/may not be helpful- I had been on Kariva/Azurette combo OCP from the age of 17 until essentially age 29 when trying to conceive. I can’t quite recall what my periods were like prior to starting OCPs, though I do remember them being on the longer end, 7-8 days maybe? I don’t remember if I spotted beforehand or not. Of course on the pill, they were regular and super predictable, lasting approx 4 days. Ever since stopping the pill, I HAVE noticed new symptoms related to my period. Namely, (severe, at times) left lower back pain that occurs 2-3 days before my period starts. I never had that on the pill. I am also experiencing what I think is chronic left ovarian pain/twinges, kind of all throughout my cycle. Not sure if this is related to scar tissue from the ectopic or what. The other problem with all of this, is I haven’t really had a NORMAL cycle without being pregnant (aside from the one month I waited after receiving methotrexate, but I wasn’t even paying attention to that cycle). So it’s really hard to pinpoint what’s exactly normal for me.
Just some thoughts of my own-
1. My husband and I are easily conceiving. We have been successful on the first try of every attempt. I have read data about women who are “ultra fertile” not being able to “weed out bad embyros” so to say, and that maybe recurrent miscarriage in these cases is not necessarily a failure to carry a pregnancy, but perhaps a failure to reject or prevent one. Though it seems like 3 failed pregnancies at this point can hardly be a coincidence or related to 3 unhealthy embryos?
2. I don’t understand why I am getting + tests after what seems like my body has already made up its mind to have a period. I am concerned about a luteal phase defect given the fact I ovulate late and start spotting 9 days later (or is this implantation spotting?). Is a LPD less likely given the fact that I am GETTING to implantation? Or can infertility/miscarriages both be a consequence of LPD?
3. I’m concerned about my low progesterone, obviously. Can this be a cause of RPL in and of itself? LPD aside?
4. I’m questioning whether I even had an ectopic in the first place (or am I having repeat ectopics? Hence my low HCGs and Progesterones?) The first pregnancy I experienced WAS different in the fact that I actually missed my period.
5. Wondering what I can next “look forward to” in terms of tests/procedures for further workup. One of my friends who’s a midwife suggested starting vaginal progesterone 3 days after ovulation – but I know the data out there on empiric progesterone is limited, so I’d hate to just TRY that without really knowing what the root cause of the problem is, especially if it means having a 4th failed pregnancy, which I cannot fathom going through. My friend felt that, because I was getting to implantation, hormone testing/HSG wouldn’t necessarily help us, and that my US would have picked up on something like an abnormal uterus. Is the progesterone something an OB might attempt as a first step prior to referring to a RE? Or even prior to further testing?
I’m feeling very alone in this process and looking for some guidance. I feel as though I, as the patient, shouldn’t have to be researching and looking up the etiologies, workup, and treatment of RPL; or looking at my pregnancy line progression worrying that it is darkening and thinking, maybe I should just start taking the leftover Progesterone I have to be safe?? I am suddenly experiencing stress and anxiety in ways I never did before (which I know isn’t helping my chances at conceiving), and just feel so obsessed with trying to get pregnant.
Looking forward to your expert opinion and thoughts, thanks again.
Carly
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: PLEASE READ!!
INTRODUCING SHER FERTILITY SOLUTIONS (SFS)
I launched Sher-Fertility Solutions (SFS) in April 2019. Through SFS, I now provide guidance, through online Skype/FaceTime consultations to people with often complex Reproductive Issues, from > 40. All consultations are followed by a detailed written report presenting my recommendations for treatment. Patients are encouraged to share this with their personal treating doctor(s) and/or to avail themselves of my hands-on IVF services, provided in batched cycles, conducted every 3 months at LAIVF in Century City, Los Angeles, CA.
If you wish to schedule a 1 hour , online consultation with me, please contact my assistant (Patti Converse) at 1-800-780-7437 or 702-533-2691. Alternatively , email Patti at concierge@SherIVF.com or enroll online at my website, http://www.SherIVF.com..
PLEASE HELP SPREAD THE WORD ABOUT SFS!
Geoff Sher
Hi Dr. Sher,
I had a fresh embryo transfer on 12/6/19. On 12/15/19, I took my first beta which was 97. Three days later I took another beta and it was 243. Four days later I took another beta and it was 923. According to the online hcg calculators, my doubling rate for 48 hours is 95%. My doctor says she’s concerned that the hcg isn’t doubling and that this could be a sign of an ectopic pregnancy or non-viable pregnancy. But what I’m reading online says that as long as hcg is doubling at a rate above 53-66%, that is normal. I have four days to wait until the ultrasound (at which time I will be 5 weeks and four days). Do you think my numbers warrant serious concern? Or is my doctor being overly cautious? If you could please let me know your thoughts I would really appreciate it. Thank you so much!
To the contrary, I would be guardedly optimistic if I were you!
Good luck!
Geoff Sher
Dear Dr Sher
my husband and I (34 and 33) had our first child 1,5 years ago and it worked immediately (2.cycle). Now, with the second child, we haven’t been able to conceive for 8 months. My hormone status and cycle monitoring are in good shape. However, my husband’s sperm analysis showed abnormal results (see below, reference values in brackets)
Abstinence: 5 days
Sample age: 23min
Volume: 8,5ml ( >1,5ml)
Color: yellow
Odor: typical
pH : 7,0 ( >7,2)
Viskosity: 3cm ( 15 Mio/ml)
Progressiv -Motility: 0 ( >32%)
Overall motility: 10 (>40%)
immobile: 90 (4%)
Defects on
Acrosome: 40
Head: 30
Middle: 10
Tail: 20
Leukocytes: 1 (<1 Mio/ml)
My husband had undescended tetsticles, for which he had surgery at the age <1 year. An ultrasound following the above sperm analysis showed that one testicle is underdeveloped, but the other one is normal, neither one of the two is undescended. We will repeat the sperm analysis, in the meantime we would like to understand the results better and ask some questions to you:
1) Do the pH values and viscosity indicate an issue with the seminal vesicle or the prostate? Or do the color and leukocyte counts indicate an inflammation?
2) Is it possible to analyse the seminal vesicle and prostate with ultrasound or any other means (to check for cysts, thrombosis, etc)?
3) For the above mentioned cases, would there even be a treatment available?
4) Which next diagnostic steps would you recommend us (besides repeating the sperm analysis) in order to understand what is wrong?
Many thanks in advance for your feedback and support. Merry Christmas and many warm regards!
1) Do the pH values and viscosity indicate an issue with the seminal vesicle or the prostate? Or do the color and leukocyte counts indicate an inflammation?
A: In my opinion, viscosity and PH do not point to a specific etiology. Nor does the leukocyte count of 1%or color suggest infection. The semen needs to be cultured aerobically, anaerobically and for ureaplasma urealyticum (requiring special transport and culture)
2) Is it possible to analyse the seminal vesicle and prostate with ultrasound or any other means (to check for cysts, thrombosis, etc)? Not really. However, testicular biopsy might be required.
3) For the above mentioned cases, would there even be a treatment available?
A: That would depend on the cause!
4) Which next diagnostic steps would you recommend us (besides repeating the sperm analysis) in order to understand what is wrong?
A: Semen culture (see above); testicular biopsy; MRI
Perhaps we should talk!
ADDENDUM: PLEASE READ!!
INTRODUCING SHER FERTILITY SOLUTIONS (SFS)
I launched Sher-Fertility Solutions (SFS) in April 2019. Through SFS, I now provide guidance, through online Skype/FaceTime consultations to people with often complex Reproductive Issues, from > 40. All consultations are followed by a detailed written report presenting my recommendations for treatment. Patients are encouraged to share this with their personal treating doctor(s) and/or to avail themselves of my hands-on IVF services, provided in batched cycles, conducted every 3 months at LAIVF in Century City, Los Angeles, CA.
If you wish to schedule a 1 hour , online consultation with me, please contact my assistant (Patti Converse) at 1-800-780-7437 or 702-533-2691. Alternatively , email Patti at concierge@SherIVF.com or enroll online at my website, http://www.SherIVF.com..
PLEASE HELP SPREAD THE WORD ABOUT SFS!
Geoff Sher
Hi Dr Sher,
I have just failed my 3rd Fet. I have elevated nk cells of 14.8 cd56, 11.5 CD 19+ cells, cd5+, tnf-a: il-10 of 42. 9 and ifn-g:il-10 of 26.8. I also have ANA of 320 tires. The first FET was done with single AB euploid blastocyst with intralipid, plaquenil, steroids, clexane, humira, baby asprin. I tend to have thinner lining so have been averaging just under 8mm at around 7.8mm.
First beta was 7, 2nd beta dropped so this round failed.
2nd FET was done with another AB blast euploid, but instead of intralipid, I did ivig. All other meds were the same as previous but with higher steroid dosage. Similar lining levels as the previous. This round failed as no hcg was present at first beta test.
3rd FET, we used 2 BB- euploid blast, same medications as previous with ivig. We managed to get my lining to just 8mm with viagra and estrogen. First beta was 15 but 2nd beta was lower to 7.
I am now at a loss for next steps. We have 5 more blasts remaining which are untested, 2 BB+, 1 BB- and 2BC
My question is does the efficacy of ivig increase with higher dosage? We used 2 bottles of kiovig every 3 weeks which I believe is 40g. I believe my dosage should be at least 58g or 60g or higher since I weight 58kg.
Also I notice my lining is much more thicker (thickest at 12mm) during a retrieval cycle. As I wish to retrieve more eggs, would it make sense to try and transfer my remaining embryos straight after a retrieval when my lining could potentially be the thickest?
It is vital that you differentiate between autoimmune and alloimmune treatment. Treatment is different. Also IVIG or Intralipid work equally well, but the latter is far less expensive, virtually free of serious side effects and is not a blood product. I no longer prescribe the former (IVIG). Also a steroid (IVIG and Intralipid treatment must be combined with prednisone or dexamethasone to be effective successful.
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.
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) Why did my IVF Fail
•Recurrent Pregnancy Loss (RPL): Why do I keep losing my PregnanciesGenetically Testing Embryos for IVF
•Staggered IVF
•Staggered IVF with PGS- Selection of “Competent” Embryos Greatly Enhances the Utility & Efficiency of IVF.
•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.
•IVF: Selecting the Best Quality Embryos to Transfer
•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?
•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!
•Natural Killer Cell Activation (NKa) and Immunologic Implantation Dysfunction in IVF: The Controversy!
•Treating Out-of-State and Out-of-Country Patients at Sher-IVF in Las Vegas
•Should IVF Treatment Cycles be provided uninterrupted or be Conducted in 7-12 Pre-scheduled “Batches” per Year
•A personalized, stepwise approach to IVF
______________________________________________________
ADDENDUM: PLEASE READ!!
INTRODUCING SHER FERTILITY SOLUTIONS (SFS)
I launched Sher-Fertility Solutions (SFS) in April 2019. Through SFS, I now provide guidance, through online Skype/FaceTime consultations to people with often complex Reproductive Issues, from > 40. All consultations are followed by a detailed written report presenting my recommendations for treatment. Patients are encouraged to share this with their personal treating doctor(s) and/or to avail themselves of my hands-on IVF services, provided in batched cycles, conducted every 3 months at LAIVF in Century City, Los Angeles, CA.
If you wish to schedule a 1 hour , online consultation with me, please contact my assistant (Patti Converse) at 1-800-780-7437 or 702-533-2691. Alternatively , email Patti at concierge@SherIVF.com or enroll online at my website, http://www.SherIVF.com..
PLEASE HELP SPREAD THE WORD ABOUT SFS!
Geoff Sher
I see no reason not to transfer embryo straight after retrieval because a lining of <8mm (at the time of the hCG trigger or the initiation of progesterone with FET)is in my opinion a contraindication for ET (fresh or frozen). I also think you should be thoroughly evaluated to differentiate between an autoimmune and an alloimmune cause o=f your NKa+. Treatment would differ and prognosis for outcome would also be different.
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.
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) Why did my IVF Fail
•Recurrent Pregnancy Loss (RPL): Why do I keep losing my PregnanciesGenetically Testing Embryos for IVF
•Staggered IVF
•Staggered IVF with PGS- Selection of “Competent” Embryos Greatly Enhances the Utility & Efficiency of IVF.
•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.
•IVF: Selecting the Best Quality Embryos to Transfer
•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?
•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!
•Natural Killer Cell Activation (NKa) and Immunologic Implantation Dysfunction in IVF: The Controversy!
•Treating Out-of-State and Out-of-Country Patients at Sher-IVF in Las Vegas
•Should IVF Treatment Cycles be provided uninterrupted or be Conducted in 7-12 Pre-scheduled “Batches” per Year
•A personalized, stepwise approach to IVF
______________________________________________________
ADDENDUM: PLEASE READ!!
INTRODUCING SHER FERTILITY SOLUTIONS (SFS)
I launched Sher-Fertility Solutions (SFS) in April 2019. Through SFS, I now provide guidance, through online Skype/FaceTime consultations to people with often complex Reproductive Issues, from > 40. All consultations are followed by a detailed written report presenting my recommendations for treatment. Patients are encouraged to share this with their personal treating doctor(s) and/or to avail themselves of my hands-on IVF services, provided in batched cycles, conducted every 3 months at LAIVF in Century City, Los Angeles, CA.
If you wish to schedule a 1 hour , online consultation with me, please contact my assistant (Patti Converse) at 1-800-780-7437 or 702-533-2691. Alternatively , email Patti at concierge@SherIVF.com or enroll online at my website, http://www.SherIVF.com..
PLEASE HELP SPREAD THE WORD ABOUT SFS!
Geoff Sher
Dr. Geoffrey Sher,
Came across your interesting blog and would like to seek your advice.
My wife (40yrs old )went through our first IVF after 3 recurrent miscarriage.
9 eggs retrieved, 8 fertilized, 7 growing as of day 3.
Day 5: 3 reach blastocyst, remaining 4 embryo appear to stop growing. only 1 of blastocyst can be freeze and biopsy.
Day 6: 2nd blastocyst can be freeze and biopsy. 3rd blastocyst was found arrested. The remain 4 embryo confirmed arrested.
Question: The lab staff find it unusual for a blastocyst to be arrested. Is it rare or or is it something common ? The other 2 blastocyst were graded 3 ( out of 1-5 rating).
My take is that they were saying that these were very poor quality blastocysts that could not survive.
Geoff Sher