Ask Our Doctors – Archive
Our Medical Directors are outstanding physicians that you will find to be very personable and compassionate, who take care to ensure that you have the most cutting-edge fertility treatments at your disposal. This is your outlet to ask your questions to the doctors.
I sometimes get electricity shock when touching metal things. If I hold may baby (10 days old) he gets the shock too. Is it dangerous?
This is likely a static electricity effect. I simply cannot advise.
Sorry!
Geoff Sher
Hi, I am 41 and about to start another IVF cycle. I have low amh (4.7). This cycle is 450 menopur, 250 orgalutran and a double ovidrel trigger which I haven’t had before. Is there anything to suggest splitting the menopur dose into am and pm will assist with follicle growth? My last cycle was 300 daily and I didn’t split, resulted in very different sizes in follicles. Is a split dose recommended? And can I please also ask your thoughts on the double ovidrel trigger? Thanks so much, Michelle
It wont make a difference whether you use a single daily administration of gonadotropins ..oe….split the dosage. As for the Ovidrel dosage , doubling to 500mcg/day is appropriate, 250mcc is half the dosage needed.
Good luck!
Geoff Sher
Hi, our biggest issue is severe male factor & after much prodding we finally did IVF-ICSI in 2014 which resulted in our daughter. 80% of the eggs resulted in day 5 blastocysts at age 33. We did a transfer of a 4AB on Halloween, my lining was 10.5mm. I should mention we did have 2 natural pregnancies in 2012 & 2013 which resulted in miscarriages (the first was a mmc at 15 weeks and was a trisomy 22 female, the second was at 6.5 weeks right before we were to start IVF). We had the immune & blood clotting tests as well as karotyping & I was diagnosed with Hashimoto’s.
Anyways, I started spotting 6 days after the embryo transfer and was told to wait, stay on meds and have a beta at 10dp5dt. The spotting and bleeding did not stop and my beta was 98.
I had another beta at 16dp5dt and the beta was <6.
I was on 100mg of Endometrium suppositories 3x per day and 2mg of estrace 2x per day. I stopped the meds on Thursday (it took 8 days to get the 2nd beta ) & AM still bleeding, not heavy.
We have a WTF appointment on December 1 with our RE but do you have any thoughts?
My FSH was 7, AMH 3 (US scale), hormones normal, thyroid under control, no uterine issues.
I just don't know why I keep having miscarriages.
Was my luteal phase not supported? Are there issues with abnormal sperm (his recent/pre IVF was his 'best' at 46million/mL but only 2% normal forms). My husband had an undescended testicle at birth and stage 1 testicular cancer in 2005.
NK cells?
Please help with some advice. I'm so sad. I thought with good eggs, a beautiful blast & a good environment this would work.
I didn't think having a baby with my husband would be this hard.
I should mention, the worst semen analysis was 10 dead sperm in the sample, the first tests were 5 million/mL with poor motility & poor shape. He’s over 40 as well.
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.
Consider contacting Julie Dahan, my patient concierge. She could guide you on how to set up an in-person or Skype consultation with me. You can reach Julie at on her cell phone or via email at any time:
Julie Dahan
•Email: Julied@sherivf.com
•Phone: 702-533-2691
?800-780-7437
Geoff Sher
I also suggest that you access the 4th edition of my book ,”In Vitro Fertilization, the ART of Making Babies”. It is available as a down-load through http://www.Amazon.com or from most bookstores and public libraries.
Dear Dr. Sher. I am scheduled for a FET next Friday (2 December 2016). My medical history (breast cancer diagnosed November 2013) means that this is my one and only chance. I have read a lot of literature regarding what to do following the embryo transfer but wondered whether you could give me your opinion on the subject? I am planning on taking the 2WW off of work due to the fact that my work can be very stressful – this is currently our busiest time of year so even more so at the current time. I have read that it is best to carry on as normal but to avoid strenuous exercise and try to avoid abdominal strain for the first few weeks. Do you have any other advice? Thank you in advance for your help.
As you yourself stated, the best advice” …”best to carry on as normal but to avoid strenuous exercise and try to avoid abdominal strain for the first few weeks”.
Good luck!
Geoff Sher
Gewoff Sher
hi. I am from South Africa. On my 2nd IUI treatment. Scan revealed 3 follicles, around 15mm -18mm. I took the hcg trigger shot on thursday at 8:30pm & had iui on sat at around 9 am. My question is – does the hcg trigger all 3 eggs to be released? And if yes, are the chances to conceive triplets high?
If you are a normal, regular ovulator, you will, more likely only ovulate from 1, following the hCG trigger. If you don’t ovulate or experience dysfunctional, you could ovulate from >1. Here is the explanantion:
Normally ovulating women usually develop a number of follicles (fluid filled spaces within the ovary (ies) that contain eggs and produce estrogen) during the first week of the menstrual cycle. All but one (and sometimes two) of the follicles fail to develop to the point of being eligible for ovulation. The process is known as Selection. It is important to recognize that in all normally ovulating women, the one or two follicles selected to ovulate will inevitably be larger than the remaining follicles, regardless of whether the woman is receiving fertility agents such as Clomiphene or Pergonal, etc. Simply put, one or two follicles will always show enhanced development over the others, and as soon as these selected follicles ovulate, all the remaining follicles are rendered incapable of following suit. As a result, normally ovulating women no not have a greater incidence of high order multiple pregnancies. In contrast, women who do not ovulate at all, and those who ovulate irregularly or dysfunctional do not have the ability to select one or two dominant follicles for ovulation. As such, following the administration of fertility drugs for ovarian stimulation, numerous follicles may develop at the same rate, and several eggs can be ovulated simultaneously. This translates into a greater chance of pregnancy, but also a greater chance of multiple pregnancies. It is interesting that almost all reported cases of high order multiple pregnancies (greater than twins) following the use of fertility drugs have occurred in women who do not ovulate normally on their own.
It follows that only those women with absent or abnormal ovulation are at-risk for high order multiple pregnancies. They, therefore, need to be counseled regarding the consequences of premature birth and the availability of selective pregnancy reduction towards the end of the third month of pregnancy. Another alternative is to avoid the issue completely by choosing in vitro fertilization (IVF), where the number of potential babies can be limited by the number of embryos transferred to the uterus.
Geoff Sher