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, I’m struggling with unexplained infertility coupled with recurrent early miscarriage (5). I have had every test that I can find and nothing untoward has shown up. FSH is around 9.8, AMH:13. One thing that sticks right out is my estradoil level, which on day 2 is 630, and day 11 is 2220. I have had the relevant MRI scans and no reason for this has been found. I did an IVF cycle with down regulation which resulted in a miscarriage, but interestingly I got pregnant the following 2 months in a row after IVF so I am convinced that my estradoil level is generally preventing me getting pregnant more often. Do you have any advice on why my e2 is so high when everything else is of a normal level? (Progesterone is normal too) and could you concur that my high E2 is related to my infertility?
I do not have an answer for your elevated E2. I would need much more information to address this authoritatively. However, here is some information on recurrent pregnancy loss:
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
My final IVF cycle at SIRM-LV commences on March 19th and concludes on April 2nd. If you are interested in undergoing a fresh IVF treatment cycle with me or if you have embryos cryopreserved at SIRM-LV and wish to undergo a Frozen Embryo Transfer (FET) prior to my departure, please contact me immediately….. My March cycle is likely to be very much in demand…….So, time is of the essence!
Following my departure from SIRM in mid-April, 2019, I will continue to provide comprehensive consultations to those of you that wish to have my guidance. Upon scheduling a SKYPE consultation with me, you will promptly receive a detailed questionnaire, along with a request that you submit available medical records for my review prior to our consultation. Additional tests and records can/will be requisitioned later, as needed. Your +/- 1 hour comprehensive SKYPE consultation will be followed by a detailed written report which you can also share with your personal Fertility Physician.
I will soon be posting a list of internationally regarded Fertility Specialists whom I endorse and who will have expressed a willingness to implement my suggested approaches, at their discretion. It is to one of these doctors that I would selectively refer you…upon request.
CONTACT INFORMATION:
•Online: Go to sherivf.com and Schedule a Skype Consultation. Upon doing so, you will be able to download a free copy of my new eBook ” Recurrent Pregnancy Loss (RPL) and Unexplained IVF Failure: The Immunologic Link”
•Phone
oIf you live in the USA or Canada: Please call 1-800-780-7437 or 702-533-2691
oIf you reside elsewhere Abroad: Please call 702-533-2691
oEmail: concierge@SherIVF.com
Please monitor this website for future announcements on further developments.
Geoff Sher
Hi Dr Sher, I read your blog post about the best protocol for older women. I am wondering if the agonist/antagonist conversion protocol (A/ACP), a modified, long pituitary down-regulation regime, augmented by adding supplementary human growth hormone (HGH) sounds right for me?
I am 42 and have never been pregnant.
My IVF history: I froze 13 mature eggs when I was 39. At 42, all 13 thawed and we had 9 embryos. No pregnancy with 2 8-cells transferred on day 3 and none of the others made it to day 5 for PGS testing. We then did a fresh cycle, but I responded too quickly to the follistim+menopur protocol (same protocol that worked when I was 39) and we triggered on day 5 to get two immature eggs. One matured in lab, fertilized, and the 4-cell day 3 transfer did not implant. We then did a suppression protocol with estrogen patch followed by clomid followed by follistim + menopur: 6 mature eggs, 4 fertilized and we transferred all 4 embryos on day 3 (3 8-cell and 1 10-cell) – no pregnancy, The 3 immature eggs matured in the lab and fertilized but did not make it to day 5 for pgs testing.
My 55-year-old husband has not had DNA frag sperm testing because the Dr said it is unnecessary as the first round of sperm testing (quantity, motility, etc) had good test results.
Any suggestions would be greatly appreciated. Thank you.
I agree with your doctor that at a DNA Fragmentation test would probably not help. And YES! I do believe the agonist/antagonist conversion protocol (A/ACP) might well be the way to go.
My final IVF cycle at SIRM-LV commences on March 19th and concludes on April 2nd. If you are interested in undergoing a fresh IVF treatment cycle with me or if you have embryos cryopreserved at SIRM-LV and wish to undergo a Frozen Embryo Transfer (FET) prior to my departure, please contact me immediately….. My March cycle is likely to be very much in demand…….So, time is of the essence!
Following my departure from SIRM in mid-April, 2019, I will continue to provide comprehensive consultations to those of you that wish to have my guidance. Upon scheduling a SKYPE consultation with me, you will promptly receive a detailed questionnaire, along with a request that you submit available medical records for my review prior to our consultation. Additional tests and records can/will be requisitioned later, as needed. Your +/- 1 hour comprehensive SKYPE consultation will be followed by a detailed written report which you can also share with your personal Fertility Physician.
I will soon be posting a list of internationally regarded Fertility Specialists whom I endorse and who will have expressed a willingness to implement my suggested approaches, at their discretion. It is to one of these doctors that I would selectively refer you…upon request.
CONTACT INFORMATION:
•Online: Go to sherivf.com and Schedule a Skype Consultation. Upon doing so, you will be able to download a free copy of my new eBook ” Recurrent Pregnancy Loss (RPL) and Unexplained IVF Failure: The Immunologic Link”
•Phone
oIf you live in the USA or Canada: Please call 1-800-780-7437 or 702-533-2691
oIf you reside elsewhere Abroad: Please call 702-533-2691
oEmail: concierge@SherIVF.com
Please monitor this website for future announcements on further developments.
Geoff Sher
Hello, I was wondering if you could help me figure out what to do. I have mosaic Turner’s syndrome and had to use an egg donor. I have a healthy son who has a tiny heart defect from a fresh transfer but my other embryos didn’t come back that great. Specifically I have one that was abnormal 70%-100% monosomy 8 with the complete chromosome gone. Do you think it’s possible for this to self correct or result in a normal baby? The genetic counselor said the pregnancy would not be viable if it truly is gone and I would miscarry or not implant. I really don’t want to give up on this one as the donation was very expensive and we can’t do it again. I tried to get an exact percentage of abnormal cells but the genetic counselor said she didn’t know. Thank you so much.
I would personally take a chance on the monosomy 8 embryo and transfer it. The worst that could happen in my opinion is that it wont implant or if it did would end up miscarrying. Conversely, it could be mosaic and autocorrect in-utero. Please keep me in the loop.
Geoff Sher
Hi Dr. Sher,
I am a hypo-hypo patient who started my IVF cycles 5 years ago. My first pregnancy was terminated via D&C as the fetus had development problems. I had intrauterine adhesion afterward which was then removed via surgery. An IUD was placed and I was on high estrogen treatment for 2 months. I undergo hysteroscopy a month later to examine whether the adhesion had reformed. The doctor removed a polyp during the hysteroscopy, which I am not sure if that’s the cause of my re-occurring adhesion months later. I then undergo another surgery with IUD place and on high estrogen for 2 months. I had
2 pregnancy afterward, 1 was a blighted ovum, another was miscarriage before it can be detected on ultrasound. I had 10 IVF cycles after but all failed. The adhesion had reappeared at the bottom of the uterus but my doctor said that shouldn’t affect pregnancy. I gone to another doctor which believe the adhesion should be removed hence I undergo another surgery, but no IUD was placed this time. I had no menstruation afterward which was due to adhesion has reformed again. I undergo another surgery, with sugi wrap placed and on high estrogen for 2 months. The sugi wrap was removed but suspect the adhesion has reappeared as I had no menstruation after the wrap is removed (the flow was good before the wrap is removed. ) . Do you suggest I should undergo another surgery to remove the adhesion? Should an IUD or balloon placed after and whether I should be on 1 or 2 months of high estrogen? I am 36yrs old now. I had 4 2mg estrofem for this cycle and my lining grows from 5mm to 1cm , my doctor suspect the adhesion has reformed around the bottom of the uterus.
Thank you very much for your opinion.
The problem is probably an implantation dysfunction and might not be reversible. The only real hope is to have the adhesions freed surgically and then to see through a estrogen/vaginal Viagra trial whether the uterine lining can be improved to >8mm. In my opinion, if it does not, then your best bet is to consider using a gestational carrier.
Geoff Sher
I have had four cycles fail bc I can’t get a normal
Embryo after pgs testing. I’ve had nine embryos go to blastocyst. Eight have come back abnormal
I have three kids. I am 40. Should I try a Mini IVF. My prior four cycles were a lot of medicine
Or should I give up.
Mini-IVF is a procedure that involves ovarian stimulation using low dosage medications (often oral drugs like clomiphene and letrozole) under the premise that it is a “safer” and less expensive than conventional gonadotropin stimulation regimes while yielding comparable success. …….. Nothing could be further from the truth. The fact is that success rates per fresh mini-IVF cycle ranges between 10% and 12%s (i.e., about one third of that which reported national average for conventional IVF performed on women under 39y of age) ). And when it comes to older women and those with diminished ovarian reserve (DOR), the success rate with mini-IVF is usually much lower still.
There can be little doubt that aside from a woman’s age, the method used for ovarian stimulation represents the most important determinant of egg/embryo quality and thus of IVF outcome. There is no single stimulation protocol that is suitable for all IVF patients. It must be individualized…. especially when it comes to women who, regardless of their age have diminished ovarian reserve (DOR) and for women over >40y of age. The reason for this is that in such cases, the pituitary gland often over-produces LH which in turn causes the ovarian stroma/theca (connective tissue) to thicken (stromal hyperplasia/hyperthecosis) and over-produce male hormones (mainly testosterone). This in turn adversely influences egg and follicle growth, resulting in poor egg/embryo “competency” and compromised IVF outcome.
So let us examine the validity of the claims made in support of mini-IVF:
1.Milder stimulation using oral agents such as clomiphene, letrozole (alone or in combination with low dosage gonadotropins (Follistim/Gonal-F/Puregon/Menopur) reduces stress on the ovaries and overall risk associated with IVF. This argument while perhaps having some merit when applied to mini-IVF conducted in younger women who also have normal ovarian reserve, does not hold water for older women and those with DOR who (s stated above) often already have excessive LH-induced ovarian testosterone production. Furthermore, addition of clomiphene and letrozole by further increasing pituitary LH (and thus ovarian testosterone) only serves to add “fuel to the fire” in such cases and Menopur which contains both LH and hCG ( that both have similar effects on ovarian testosterone production), if administered in large amounts (>75U per day) can also do harm in my opinion.
2.Women with DOR will respond better to “milder stimulation” and egg quality will so be enhanced. This assertion borders on the ridiculous. It is like saying that applying less force to a heavier object will increase the likelihood of moving it”. That is simply not how FSH stimulates follicle development. You see…the cell membranes that envelop the follicular granulosa cells that line the inside surface of ovarian follicles have on their surfaces, a finite number of FSH receptors. FSH molecules attach to these receptors and mediate intracellular events that lead to granulosa cell proliferation with production of estradiol and the concurrent development of the egg (oogenesis) that is attached to the inner wall of the follicle. Once all the FSH receptors on the cell membranes are saturated, any residual FSH is discarded. This is why, when it comes to older women and women with DOR whose granulose cell membranes harbor fewer FSH receptors, it is virtually impossible to overstimulate them. Excessive FSH will simply be rejected and discarded.
3. Use of fewer drugs translates into lower cost. This would be true, were it not for the fact that success rates with mini-IVF across the board are much lower than with conventional ovarian stimulation. More important is the fact that the cost of IVF should be expressed in terms of “the cost of having a baby” rather than “cost per cycle of treatment”. When this is taken into account the cost associated with mini-IVF will b be significantly higher than conventional IVF. Then there is the additional emotional cost associated with a much higher IVF failure rate with mini-IVF.
4.Mini-IVF is less technology driven, less stressful and easier to execute. This assertion is in my opinion also without merit. Aside from reduced cost of medications, the same monitoring and laboratory procedures are needed for mini-IVF as with conventional treatment.
What is the best approach? When it comes to older women and those with DOR, it is in my opinion preferable to use a long pituitary down-regulation protocol with conversion from an I.M agonist (e.g. Lupron or Buserelin) to an antagonist such as Cetrotide/Orgalutron or Ganirelix (the agonist/antagonist conversion protocol) augmented with human growth hormone (HGH) and/or estrogen priming and combing this “embryo banking” over several cycles. In such cases preimplantation genetic screening (PGS) can be incorporated to help select the most “competent” embryos for transfer.
What about younger women with normal or increased ovarian reserve? If mini-IVF has any role at all, it could be in young women who have normal or increased ovarian reserve. I do not o not advocate aggressively stimulating the ovaries of younger women who have normal or increased ovarian reserve (as assessed by basal FSH, AMH and estradiol) simply to try and access more eggs. In fact, such an approach is neither safe nor acceptable. In such women it is often wiser to use lower dosage stimulation to try and prevent the development of severe ovarian hyperstimulation syndrome (OHSS) which aside from putting the woman at severe risk of (sometimes) life-endangering complications, can also compromise egg/embryo quality. However, it is my fervent belief that in such women, the preferred approach to ovarian stimulation is through the use of low dosage FSHr-dominant gonadotropins (rather than oral agents such as clomiphene or letrozole and/or high dosage Menopur). This approach is referred to as Micro-IVF.
Here is the protocol I advise for women who have adequate ovarian reserve.
My advice is to use a long pituitary down regulation protocol starting on a BCP, and overlapping it with Lupron 10U daily for three (3) days and then stopping the BCP but continuing on Lupron 10u daily (in my opinion 20U daily is too much) and await a period (which should ensue within 5-7 days of stopping the BCP). At that point an US examination is done along with a baseline measurement of blood estradiol to exclude a functional ovarian cyst and simultaneously, the Lupron dosage is reduced to 5U daily to be continued until the hCG (10,000u) trigger. An FSH-dominant gonadotropin such as Follistim, Puregon or Gonal-f daily is started with the period for 2 days and then the gonadotropin dosage is reduced and a small amount of menotropin (Menopur—no more than 75U daily) is added. This is continued until US and blood estradiol levels indicate that the hCG trigger be given, whereupon an ER is done 36h later. I personally would advise against using Lupron in “flare protocol” arrangement (where the Lupron commences with the onset of gonadotropin administration.
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
• Use of GnRH Antagonists (Ganirelix/Cetrotide/Orgalutron) in IVF-Ovarian Stimulation Protocols.
• Anti Mullerian Hormone (AMH) Measurement to Assess Ovarian Reserve and Design the Optimal Protocol for Controlled Ovarian Stimulation (COS) in IVF.
• 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
• “Triggering” Egg Maturation in IVF: Comparing urine-derived hCG, Recombinant DNA-hCG and GnRH-agonist:
My final IVF cycle at SIRM-LV commences on March 19th and concludes on April 2nd. If you are interested in undergoing a fresh IVF treatment cycle with me or if you have embryos cryopreserved at SIRM-LV and wish to undergo a Frozen Embryo Transfer (FET) prior to my departure, please contact me immediately….. My March cycle is likely to be very much in demand…….So, time is of the essence!
Following my departure from SIRM in mid-April, 2019, I will continue to provide comprehensive consultations to those of you that wish to have my guidance. Upon scheduling a SKYPE consultation with me, you will promptly receive a detailed questionnaire, along with a request that you submit available medical records for my review prior to our consultation. Additional tests and records can/will be requisitioned later, as needed. Your +/- 1 hour comprehensive SKYPE consultation will be followed by a detailed written report which you can also share with your personal Fertility Physician.
I will soon be posting a list of internationally regarded Fertility Specialists whom I endorse and who will have expressed a willingness to implement my suggested approaches, at their discretion. It is to one of these doctors that I would selectively refer you…upon request.
CONTACT INFORMATION:
•Online: Go to sherivf.com and Schedule a Skype Consultation. Upon doing so, you will be able to download a free copy of my new eBook ” Recurrent Pregnancy Loss (RPL) and Unexplained IVF Failure: The Immunologic Link”
•Phone
oIf you live in the USA or Canada: Please call 1-800-780-7437 or 702-533-2691
oIf you reside elsewhere Abroad: Please call 702-533-2691
oEmail: concierge@SherIVF.com
Please monitor this website for future announcements on further developments.
Geoff Sher