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.
Hello Dr. Sher,
I had asked the same question(s) I am about to ask earlier this month, but I never did see my post show up on this page. Maybe it did not go through. Sorry in advance if I just missed it!
I am currently on my third consecutive cycle of IUI. I actually will be testing this Saturday. Obviously the previous 2 cycles were unsuccessful. All have been Clomid cycles (Clomid taken days 3-7 of my cycle, 100mg each day), have responded well every time, triggered with Pregnyl each time approximately days 11-12, and IUIs happening approximately days 12-14. First IUI I went back 48 hours after IUI to confirm ovulation, and always have started progesterone suppositories that evening, and stopping when the pregnancy tests have been negative. In my opinion they have been great cycles, just unsuccessful. I was diagnosed with stage IV endometriosis at the end of March 2019 at age 29 (I will be 30 in March). My RE removed all that he could, but I did NOT lose any organs (I DID have 1 chocolate cyst). Both of my tubes were open at the time of my surgery. Surgery has improved my symptoms tremendously aside from the infertility. I also have slight hypothyroidism, diagnosed approximately November 2017 and I take 30mg of NP Thyroid daily. I also had some chronically low vitamin D levels for awhile, but I have since made an enormous effort to keep my vitamin D up. I also take a prenatal daily and have been doing so for months. I have never been pregnant to my knowledge, but I do think I may have had a blighted ovum in June 2015. My question for you is 1) is there anything else that I could be doing to figure out why I am still not getting pregnant (provided my upcoming test is negative again), and 2) is it worth my while to continue with any more IUI cycles, or would you say that I am a good IVF candidate?
Thank you for your time!
1.Both endometriosis and autoimmune hypothyroidism are often associated with an immunologic implantation dysfunction and this could (at least in part) explain your failures
2. Endometriosis (especially in the advanced stages) in my opinion, represents a relative contraindication to doing IUI…see below:
ENDOMETRIOSIS:
Endometriosis is a complex condition where, the lack or relative absence of an overt anatomical barrier to fertility often belies the true extent of reproductive problem(s).
All too often the view is expounded that the severity of endometriosis-related infertility is inevitably directly proportionate to the anatomical severity of the disease itself, thereby implying that endometriosis causes infertility primarily by virtue of creating anatomical barriers to fertilization. This over-simplistic and erroneous view is often used to support the performance of many unnecessary surgeries for the removal of small innocuous endometriotic lesions, on the basis of such “treatment” evoking an improvement in subsequent fertility.
The annual birth rate for normally ovulating women, free of any pelvic pathology (including mild endometriosis, who are having regular intercourse with fertile male partners, timed to coincide with ovulation differs with the age of the woman. For women under 35yrs it is about 80% .For those 35-40yrs of age, is about 50-60% and for women in their early 40’s the comparable annual rate is approximately 20-25% In contrast women in similar age categories who have even the mildest degree of endometriosis can expect a 3-4 fold reduction in annual birth rate.
It is indeed indisputable that even the mildest form of endometriosis can compromise fertility. It is equally true that, mild to moderate endometriosis is by no means a cause of absolute “sterility”. Rather, when compared with normally ovulating women of a similar age who do not have endometriosis, women with mild to moderate endometriosis are about three to four times less likely to have a successful pregnancy. Two important reasons for such reduction in fertility potential are:
•The existence of endometriotic deposits in the pelvis is associated (in all cases) with the presence “toxins” in the pelvic secretions. This significantly reduces the fertilization potential of eggs as they pass from the ovary to the fallopian tube via the pelvic cavity, and…..
•In about one third (1/3)of cases endometriosis almost certainly involves an immune implantation dysfunction (IID) such that the uteri od such women tends to reject the embryo (fertilized egg) as it attempts to gain attachment to the uterine lining (endometrium).
What about Surgery, ovulation induction with fertility agents and intrauterine (artificial) insemination- IUI for treating women who have early endometriosis?
All women with endometriosis have toxins in their pelvic secretions that, compromise the ability of sperm to fertilize eggs that pass through this environment from the ovary (ies) to reach sperm in the fallopian tube(s).This dramatically reduces fertilization potential of such eggs (by a factor of 4-6 fold) It serves to explain why potentially all women with endometriosis have reduced fecundity (reproductive potential) and. It also serves to explain why the use of tubal surgery, fertility drugs and/or intrauterine insemination (IUI) will likely not improve fecundity over no treatment at all and why in normally ovulating women, when pregnancy ensues following such approaches it in all likelihood occurred in spite of, rather than due to such treatment. The only way to avoid this effect is through by-passing this toxic pelvic environment by extracting the eggs before4 they are exposed to the toxic pelvic secretions…IOW, IVF.
Endometriosis and an immunologic implantation dysfunction (IID):
The second factor that must be carefully evaluated in women with early endometriosis is the possibility that she might have an immunologic implantation dysfunction (IID) linked to activation of uterine natural killer cells (NKa). Accordingly, in my opinion, all women who have symptoms suggestive of endometriosis (heavy and painful menstruation, pain with ovulation, pain with deep penetration during intercourse, unexplained infertility and failure to conceive after repeated attempts at IUI or IVF) should be tested for NKa using the K-562 target cell test and if this indicated NKa, the treatment would involve Intralipid infusions, steroids and possible heparinoids (e.g. Clexane and Lovenox). Tests for IID should only be done in a reproductive immunology reference lab capable of performing these tests with the required sensitivity currently exist in the U.S.A. There are to my knowledge fewer than a half dozen such reference laboratories in the United states..
How should fertility treatment be planned for in women with Early Endometriosis?
Since in the absence of an IID, women ovulating women who have early endometriosis (and fertile partners) can and do conceive spontaneously albeit much more difficult to succeed. Thus, since alternatives such as ovulation induction, surgery and/or IUI offer little if any advantage over no treatment at all, younger women (under 35y) who have no diminished ovarian reserve (normal AMH) and no IID, can elect to take a “wait and see approach for a year or two at which time if no pregnancy occurs IVF would become the treatment of choice. However, if there is an associated IID or a male infertility component to boot, they are best advised to go directly to IVF which is much likely to be successful”. However, if such women, in addition have diminished ovarian reserve (such that time3 might be running out on their fecundity), and IID or a concomitant male factor component they Are best advised to go directly to IVF.
Older women (over 35yrs) who have endometriosis-related infertility, do not have time to waste and should, in my opinion regard IVF as a first line approach, regardless of their immunologic status.
AUTOIMMUNE tHYROID DISEASE
Between 2% and 5% of women of the childbearing age have reduced thyroid hormone activity (hypothyroidism). Women with hypothyroidism often manifest with reproductive failure i.e. infertility, unexplained (often repeated) IVF failure, or recurrent pregnancy loss (RPL). The condition is 5-10 times more common in women than in men. In most cases hypothyroidism is caused by damage to the thyroid gland resulting from of thyroid autoimmunity (Hashimoto’s disease) caused by damage done to the thyroid gland by antithyroglobulin and antimicrosomal auto-antibodies.
The increased prevalence of hypothyroidism and thyroid autoimmunity (TAI) in women is likely the result of a combination of genetic factors, estrogen-related effects and chromosome X abnormalities. This having been said, there is significantly increased incidence of thyroid antibodies in non-pregnant women with a history of infertility and recurrent pregnancy loss and thyroid antibodies can be present asymptomatically in women without them manifesting with overt clinical or endocrinologic evidence of thyroid disease. In addition, these antibodies may persist in women who have suffered from hyper- or hypothyroidism even after normalization of their thyroid function by appropriate pharmacological treatment. The manifestations of reproductive dysfunction thus seem to be linked more to the presence of thyroid autoimmunity (TAI) than to clinical existence of hypothyroidism and treatment of the latter does not routinely result in a subsequent improvement in reproductive performance.
It follows, that if antithyroid autoantibodies are associated with reproductive dysfunction they may serve as useful markers for predicting poor outcome in patients undergoing assisted reproductive technologies.
Some years back, I reported on the fact that 47% of women who harbor thyroid autoantibodies, regardless of the absence or presence of clinical hypothyroidism, have activated uterine natural killer cells (NKa) cells and cytotoxic lymphocytes (CTL) and that such women often present with reproductive dysfunction. We demonstrated that appropriate immunotherapy with IVIG or intralipid (IL) and steroids, subsequently often results in a significant improvement in reproductive performance in such cases.
The fact that almost 50% of women who harbor antithyroid antibodies do not have activated CTL/NK cells suggests that it is NOT the antithyroid antibodies themselves that cause reproductive dysfunction. The activation of CTL and NK cells that occurs in half of the cases with TAI is probably an epiphenomenon with the associated reproductive dysfunction being due to CTL/NK cell activation that damages the early “root system” (trophoblast) of the implanting embryo. We have shown that treatment of those women who have thyroid antibodies + NKa/CTL using IL/steroids, improves subsequent reproductive performance while women with thyroid antibodies who do not harbor NKa/CTL do not require or benefit from such treatment
IUI:
It is hard for me to believe that more than three decades have flown by since I first introduced intrauterine insemination into the clinical arena (Journal of Fertility & Sterility, April, 1984). At that time and for more than 2 decades thereafter, I held the strong belief that IUI would provide a less expensive, safe and equally successful alternative to IVF in cases where the woman had at least one (1) patent Fallopian tube…. How wrong I was! In my defense however, let me say that in the 1980’s and 90’s the reported National IVF success rate was under 15% while y IVF success rates are now often 4 or even 5 times higher.
Today I believe that IUI is being over-used, is not nearly as beneficial as I once thought and that there are (often ignored) serious down-sides to its use. Here is one important example: Women who fail to ovulate or ovulate dysfunctionally, often respond to controlled ovarian stimulation (COS) by the releasing (ovulating) of several eggs at a time. Since unless IVF is used, it is not possible to control/regulate the number of embryos reaching the uterus, the risk of high-order multiple pregnancies (triplets or greater) is far greater with IUI. And, multiple pregnancies (especially triplets or greater) carry a very high maternal and neonatal risk.
Here are a few of the misperceptions about the use of IUI:
1)IUI is a “cost saver”. However, given the fact that IVF is at least 3-4 times more likely to be successful, when one looks at cost per baby (rather than cost per procedure) this turns out to be a fallacy. But cost also comes in the form of emotional currency and this needs to be measured in terms of the much lower chance of success with IUI.
2)”IUI is less invasive than IVF”… ….True! However aside from the surgical egg retrieval (which is a very safe procedure in the right hands/setting), IUI with gonadotropins requires largely the same drugs, preparation and monitoring as does IVF and the success rate is several fold lower than IVF.
3)The use of oral Clomiphene Citrate for IUI- COS provides the same success rates as does Gonadotropin-IUI. This is absolutely incorrect. In fact the IUI success rate with clomiphene is about 30% lower than when gonadotropins are used.
4)Natural cycle IUI has benefit: This is only true when frozen donor sperm is used for inseminations and in the isolated cases where there is non-immunologic cervical hostility to sperm. In all other cases, COS is needed to improve success.
5)IUI can be used in cases of Embryo Implantation Dysfunction: Given the complexity of treatment is in cases where a thin uterine lining, significant uterine anatomical disease or immunologic implantation dysfunction (IID) prevents a healthy pregnancy, it is my opinion that IVF is the preferred primary approach.
6)IUI can supplant or replace IVF in all cases where there is patency of at least 1 Fallopian tube. However, contrary to popular belief, there is no evidence that IUI improves pregnancy potential in cases of:
a.Moderate or severe male factor infertility
b.Endometriosis with patent Fallopian tubes. Since inseminating sperm does not overcome the main impediment to fertility, i.e., a “toxic” peritoneal factor that compromises sperm penetrating the egg envelopment).
c.Older women (over 40y) where the IUI pregnancy yield is only about 2% per treatment cycle.
Upon Honest Reflection:
Unfortunately, too many physicians who should (and alas often do) know better, still liberally recommend IUI preferentially in cases of moderate or severe male infertility, older infertile women or those with diminished ovarian reserve (DOR), cases of endometriosis or where there is clear evidence of an anatomical r immunologic implantation issue. Such women would be much better advised to go directly to IVF but find themselves attracted to what they erroneously consider to be a much lower cost alternative.
Then there is the fact that many infertile patients, erroneously believing that IUI is less risky that IVF, provides an equivalent chance of success, and comes at a much lower price tag, put undue pressure on their physicians to first try the former several times before resorting to the latter.
To make matters worse, many misguided insurance providers (purely for economic reasons) demand that their female clients who have at least 1 patent Fallopian tube, first undergo several unsuccessful attempts at IUI before becoming eligible for IVF. And they often take this position regardless of cast iron indications that IVF should be the primary treatment of choice.
In summary, it is my opinion that IUI is presently an over-prescribed treatment. As such, we as physicians need to rethink the basis upon which we recommend IUI and educate our patients appropria
ADDENDUM: PLEASE READ!!
INTRODUCING SHER FERTILITY SOLUTIONS (SFS)
Founded in April 2019, Sher Fertility Solutions (SFS) offers online (Skype/FaceTime) consultations to patients from > 40 different countries. All consultations are followed by a detailed written report presenting my personal recommendations for treatment of what often constitute complex Reproductive Issues.
Patients are encouraged to share the information I provide, with their treating Physicians and/or to avail themselves of my personal hands-on services, provided through batched IVF cycles that I conduct every 3 months at Los Angeles IVF (LAIVF) Clinic, Century City, Los Angeles, CA.
If you wish to schedule an online consultation with me, please contact my assistant (Patti Converse) by phone (800-780-7437/702-533-2691), email (concierge@SherIVF.com) or, enroll online on then home-page of my website (www.SherIVF.com).
PLEASE SPREAD THE WORD ABOUT SFS!
Geoff Sher
Hi Dr Sher,
I am about to undergo a new round of IVF. Previously I have undergone a lot of IVF treatment as I was diagnosed with PCOS, at the time I was 30, with a BMI of 20, I have always been healthy and fit, never had any weight issues.
In total I have so far done…2 x IVF rounds which showed lots of follicles but all were empty on retrieval, 2 x IVM rounds which resulted in a few embryos which ended up without a pregnancy. 1 x IVF with a double trigger which finally resulted in 9 eggs and 4 embryos, the last one is now my son, I severely overstimulated from this egg collection, we have no embryos left.
We are about to undertake another round and my fertility doctor thinks not only do I have PCOS but that I also have an LH receptor defect. She has recommended an antagonist protocol with menupour and gonal F with a double trigger. Do you have any other thoughts as she has said my LH condition is very rare and there isn’t a lot of info out there. I am so worried that we won’t get any more eggs or embryos and want to be as informed as possible about my condition.
I live in Auckland, NZ.
I have responded previously to this post!
Geoff Sher
What are your thoughts on stem cell therapy or the use of tamoxifen for the treatment of thin endometrium? Thank you for the good work you do for others!
I see no way either could help. Tamoxifen is an anti-estrogen and would thin the lining even more.
Geoff Sher
My beta HCG levels at 6dp5dt were 49. Today’s blood draw (14dp5dt) indicate my levels went up to 1976. Is this type of a rapid rise normal for a singleton pregnancy? Does this type of increase indicate multiples?
It could be normal for a singleton but a multiple is definitely on the cards for you!
Good luck!
Geoff Sher
Hello Dr. Sher,
I am 35 years old. Was pregnant 3 times 5-6 years ago. Unfortunately, the first 2 pregnancies resulted in MMCs, but then I had a healthy baby. All 3 were conceived with no problems. We are now trying for #2, and it appears that I may have issues with my cycle/ovulation. I did bloodwork and the results are below:
testosterone 29 ng/dL
testosterone free 0.35 ng/dL
AMH 0.35ng/mL
FSH 5.5 mU/mL
Hydroxyprogesterone 17.72 ng/dL
prolactin 8.2-8.7 ng/mL
TSH 2.540 uU/mL
estradiol 17B 44 pg/mL
LH 1.6 mU/mL
DHEA-S 339.9 ug/dL
t4 7.6 ug/dL
The doctor told me that my AMC is low and suggested a possible DOR. She also mentioned that FSH is “good” and that’s a good sign. My understanding is that my DHEA-S is also elevated.
I was advised to try chlomid (not sure what the dosage is) D3-7. Take dexamethasone to lower the DHEA-S from day 3 to ovulation. I would go to an US to measure follicles on day 12-14, and, if everything looks good, trigger with Ovidrel 250 mcg/5ml.
Would you recommend anything different?
Thank you very much for your answer!!!
With that degree of DOR (normal AMH=>2.0ng/ml) I would consider doing IVF. But before doing so, I would undergo an evaluation for an anatomical and immunologic implantation dysfunction.
Women who (regardless of age) have diminished ovarian reserve (DOR) have a reduced potential for IVF success. Much of this is due to the fact that such women tend to have increased production, and/or biological activity, of LH. This can result in excessive ovarian male hormone (predominantly testosterone) production. This in turn can have a deleterious effect on egg/embryo “competency”.
While it is presently not possible by any means, to reverse the effect of DOR, certain ovarian stimulation regimes, by promoting excessive LH production (e.g. short agonist/Lupron- “flare” protocols, clomiphene and Letrozole), can in my opinion, make matters worse. Similarly, the amount/dosage of certain fertility drugs that contain LH/hCG (e.g. Menopur) can have a negative effect on the development of the eggs of older women and those who have DOR and should be limited.
I try to avoid using such protocols/regimes (especially) in women with DOR, favoring instead the use of the agonist/antagonist conversion protocol (A/ACP), a modified, long pituitary down-regulation regime, augmented by adding supplementary human growth hormone (HGH). I further recommend that such women be offered access to embryo banking of PGS (next generation gene sequencing/NGS)-selected normal blastocysts, the subsequent selective transfer of which by allowing them to capitalize on whatever residual ovarian reserve and egg quality might still exist and thereby “make hay while the sun still shines” could significantly enhance the opportunity to achieve a viable pregnancy
Please visit my new Blog on this very site, www. SherIVF.com, find the “search bar” and type in the titles of any/all of the articles listed below, one by one. “Click” and you will immediately be taken to those you select. Please also take the time to post any questions or comments with the full expectation that I will (as always) respond promptly
•Controlled Ovarian Stimulation (COS) for IVF: Selecting the ideal protocol
•IVF: Factors Affecting Egg/Embryo “competency” during Controlled Ovarian Stimulation(COS)
•The Fundamental Requirements For Achieving Optimal IVF Success
•Ovarian Stimulation for IVF using GnRH Antagonists: Comparing the Agonist/Antagonist Conversion Protocol.(A/ACP) With the “Conventional” Antagonist Approach
•Anti Mullerian Hormone (AMH) Measurement to Assess Ovarian Reserve and Design the Optimal Protocol for Controlled Ovarian Stimulation (COS) in IVF.
•The “Biological Clock” and how it should Influence the Selection and Design of Ovarian Stimulation Protocols for IVF.
• A Rational Basis for selecting Controlled Ovarian Stimulation (COS) protocols in women with Diminished Ovarian Reserve (DOR)
•Diagnosing and Treating Infertility due to Diminished Ovarian Reserve (DOR)
•Controlled Ovarian Stimulation (COS) in Older women and Women who have Diminished Ovarian Reserve (DOR): A Rational Basis for Selecting a Stimulation Protocol
•Human Growth Hormone Administration in IVF: Does it Enhances Egg/Embryo Quality and Outcome?
•The BCP: Does Launching a Cycle of Controlled Ovarian Stimulation (COS). Coming off the BCP Compromise Response?
•Blastocyst Embryo Transfers Should be the Standard of Care in IVF
•Frozen Embryo Transfer (FET) versus “Fresh” ET: How to Make the Decision
•Frozen Embryo Transfer (FET): A Rational Approach to Hormonal Preparation and How new Methodology is Impacting IVF.
•Staggered IVF: An Excellent Option When. Advancing Age and Diminished Ovarian Reserve (DOR) Reduces IVF Success Rate
•Embryo Banking/Stockpiling: Slows the “Biological Clock” and offers a Selective Alternative to IVF-Egg Donation.
•Preimplantation Genetic Testing (PGS) in IVF: It Should be Used Selectively and NOT be Routine.
•Preimplantation Genetic Sampling (PGS) Using: Next Generation Gene Sequencing (NGS): Method of Choice.
•PGS in IVF: Are Some Chromosomally Abnormal Embryos Capable of Resulting in Normal Babies and Being Wrongly Discarded?
•PGS and Assessment of Egg/Embryo “competency”: How Method, Timing and Methodology Could Affect Reliability
•Treating Out-of-State and Out-of-Country Patients at Sher-IVF in Las Vegas:
•Traveling for IVF from Out of State/Country–
•A personalized, stepwise approach to IVF
•How Many Embryos should be transferred: A Critical Decision in IVF.
•The Role of Nutritional Supplements in Preparing for IVF
•Premature Luteinization (“the premature LH surge): Why it happens and how it can be prevented.
•IVF Egg Donation: A Comprehensive Overview
___________________________________________________
ADDENDUM: PLEASE READ!!
INTRODUCING SHER FERTILITY SOLUTIONS (SFS)
Founded in April 2019, Sher Fertility Solutions (SFS) offers online (Skype/FaceTime) consultations to patients from > 40 different countries. All consultations are followed by a detailed written report presenting my personal recommendations for treatment of what often constitute complex Reproductive Issues.
Patients are encouraged to share the information I provide, with their treating Physicians and/or to avail themselves of my personal hands-on services, provided through batched IVF cycles that I conduct every 3 months at Los Angeles IVF (LAIVF) Clinic, Century City, Los Angeles, CA.
If you wish to schedule an online consultation with me, please contact my assistant (Patti Converse) by phone (800-780-7437/702-533-2691), email (concierge@SherIVF.com) or, enroll online on then home-page of my website (www.SherIVF.com).
PLEASE SPREAD THE WORD ABOUT SFS!
Geoff Sher