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.
In your opinion, can HGH supplementation increase IVF success one or more months prior to stimulation? Thank you K
No!
Geoff Sher
I understand the literature with regard to inaccurate AMH testing during pregnancy. I can’t find references regarding when AFCs might return to normal. Please provide your opinion or references?
AFC measured at the beginning of a cycle, while fluctuating slightly from cycle to cycle, will in my opinion, not increase over all. And there is no known treatment that will improve ovarian reserve.
Please visit my new Blog on this very site, http://www.DrGeoffreySherIVF.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
•Ovarian Stimulation for IVF using GnRH Antagonists: Comparing the Agonist/Antagonist Conversion Protocol.(A/ACP) With the“Conventional” Antagonist Aproach
•IVF: Factors Affecting Egg/Embryo “competency” during Controlled Ovarian Stimulation(COS)
•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.
•Diagnosing and Treating Infertility due to Diminished Ovarian Reserve (DOR)
•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?
•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 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?
•Traveling for IVF from Out of State/Country–
•A personalized, stepwise approach to IVF
•The Role of Nutritional Supplements in Preparing for IVF
•The Fundamental Requirements For Achieving Optimal IVF Success
I invite you to arrange to have a Skype or an in-person consultation with me to discuss your case in detail. If you are interested, please contact Julie Dahan, at:
Email: Julied@sherivf.com
OR
Phone: 702-533-2691
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.
Geoff Sher
Background: My maternal grandmother gave birth to healthy children at ages forty and forty-seven before undergoing oopherctomy to prevent further pregnancies (she had practiced FAM and was successful until the second pregnancy, but delayed in attempts due to WW.) My mother had regular cycles of 30-32 days until age 61 (tubal ligation at age 35.) She was monitored closely and still menstruated to age 62. At age 63 she was diagnosed and succumbed to a brain tumor, though continued menses until death.)
Question: Can you direct me to recent studies that link fertility/fecundity based on maternal age of menopause? Your personal opinion?
More and more women are deciding based upon personal preference and professional necessity, to postpone having a family to a later age. In fact, very recently, Janet Jackson (49Y) was in the news stating that she was cancelling her tour to prepare for treatment needed to have a baby. This prompted me to write this article on IVF in women of more advanced age.
The truth is that hardly a day goes by when I am not asked the question of “How old is too old to do IVF? The standard answer is that for women under 43Y provided that they have an adequate number of eggs (ovarian reserve) IVF with own eggs is definitely an option. After 43y the percentage chance that an IVF cycle (where the woman uses her own eggs) will result in a live birth, declines to the single digit range and after age 45Y it falls to well under 5% per cycle, making the use of an egg donor, the only rational choice.
Any decision of when/ whether a woman’s age should affect a medical decision on whether or not to proceed to IVF, should also take into consideration: 1) the increasing incidence of pregnancy complications with advancing age 2) The risk to the baby k of poor intrauterine development and premature birth …both with their risks,3) ethical factors such as age and its effect on projected life span as well as the physical, emotional and financial ability to provide for the needs of the child.
BUT it is not as simple as that! I will never forget a couple that travelled from Munich Germany to consult with me re IVF with Egg Donation about 20 years ago. The lady, who will here be referred to as (JS) was 53 years of age and her husband (PL) was 44. At that time we had a general policy not treat women over 50 years of age. When I informed her of this, she became very agitated. She responded that she was in perfect health, while her husband suffered from moderately severe hypertension and type 2 diabetes. She asserted that had the ages been reversed (i.e. if she were 44Y and he, 53Y) we would never have rejected them. She went on to insist that the ruling amounted to sexual discrimination….and you know what? She was right! I suggested that the couple personally present their argument to our Ethics Advisory Board…which they did. The board authorized me to perform IVF with egg donation. I did so and subsequently transferred two embryos to PL’s uterus. She conceived and gave normal vaginal birth (at full term) to two healthy girls. I have since heard regularly from this couple, receiving family photographs, virtually every year. The two girls are now both in college in. Sadly PL passed away about 3 years ago and JS very recently got remarried. The new family is thriving.
Any woman, regardless of age, given access to “competent” eggs/embryos whether own egg or donor-derived, who has a receptive uterus (her own, or that of a gestational carrier), is, capable of achieving motherhood through IVF. This ability is of course predicated upon the patient having access to a full spectrum of options.
Herewith, a few basic considerations:
1.Access to at least one “competent” embryo. It is a fact that as women advance beyond their mid-thirties, both the number and chromosomal integrity of their eggs, will inevitably decline. At age 30Y about 1:2 are chromosomally numerically normal (euploid) and “competent”, upon fertilization to implant in the uterus and propagate healthy babies. By age 40Y about 1:6 eggs are euploid and by the 42nd year, only about 1:10 will be “competent”. By the time the woman reaches age 45, only about 1: 25 harvested eggs will be euploid
Simultaneously, as the woman reaches her 40’s, the number of eggs remaining in her ovaries (her ovarian reserve) will start to decline This diminishing ovarian reserve (DOR) will be reflected in her basal blood FSH level rising progressively and her blood antimullerian hormone (AMH) level dropping. What this means is that the woman’s pregnancy potential drastically declines as she emerges from her 30’s into her 40’s.
The combination of age-related egg “competency” and ovarian reserve is is defined as the “biological clock” By the time the average woman reaches 43y, both these component parts of the “biological clock” will usually have declined substantially such that after 43 years of age, she would be best advised to preferentially choose egg donation. The transfer of a single advanced embryo (blastocyst) to the uterus of a 43 year old woman, will likely yield less than a 10% chance of a baby. Conversely, a similar looking blastocyst found through chromosomal testing or PGS (using next generation Gene sequencing or NGS) to be euploid and “competent” could allow the same woman a 40-50% chance of a live birth. It thus follows that for women with such declining fertility potential, NGS embryo testing with “banking” (stockpiling) of several embryos over multiple IVF cycles will at the time of transfer to the uterus, dramatically improve the odds of success.
2.A receptive uterus: For an embryo to propagate a viable pregnancy the uterus needs to be as anatomically normal, its endometrial lining needs to develop normally in response to estrogen and any underlying immunologic implantation dysfunction must be identified and corrected. Conditions such as uterine fibroids and adenomyosis are more prevalent in older women. And post-menopausal women who are estrogen depleted will find their uteri shrinking and the endometrial lining becoming ever less responsive to estrogen. It is important in such cases to prescribe estrogen hormone replacement therapy for 2-3 months, prior to performing embryo transfer.
3.A healthy parturient, who is capable of carrying a baby to term. The Hippocratic Oath demands that physicians knowingly never put patients in harms way. Since pregnancy is inevitably associated with increasing maternal risk as the woman ages, it is important prior to embarking on fertility treatment in such cases, to perform a thorough physical examination and a barrage of tests that includes (but are not limited to) EKG; Chest X-ray; Blood chemistry (BUN, electrolytes, creatinine, liver enzymes, lipid profile, glucose etc..); mammogram and PAP smear. It is also important to explain to the patient/couple.
4.A medical and laboratory team with the necessary experience/expertise, and with ready access to the most advanced options such as:
a. Egg Donation
b.Gestational Surrogacy
c.Donor sperm (if needed)
d.Genetic embryo selection (using PGS)
e.Gestational surrogacy.
When it comes to a “cut off” for IVF eligibility, age is an important consideration and the risk/benefit of any particular course of treatment needs to be critically addressed with patients but there can in my opinion, not be any hard and fast rule. In the final analysis, each case must be considered on its own merit. As physicians we have the responsibility of providing patients with information needed to make a decision without imposing our will upon them.
Please visit my new Blog on this very site, http://www.DrGeoffreySherIVF.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
•Ovarian Stimulation for IVF using GnRH Antagonists: Comparing the Agonist/Antagonist Conversion Protocol.(A/ACP) With the“Conventional” Antagonist Aproach
•IVF: Factors Affecting Egg/Embryo “competency” during Controlled Ovarian Stimulation(COS)
•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.
•Diagnosing and Treating Infertility due to Diminished Ovarian Reserve (DOR)
•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?
•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 Sampling (PGS) Using: Next Generation Gene Sequencing (NGS): Method of Choice.
•Traveling for IVF from Out of State/Country–
•A personalized, stepwise approach to IVF
•Advancing Age of the Woman and IVF: How Old is too old?
I invite you to arrange to have a Skype or an in-person consultation with me to discuss your case in detail. If you are interested, please contact Julie Dahan, at:
Email: Julied@sherivf.com
OR
Phone: 702-533-2691
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.
Geoff Sher
Please forgive my rapid barrage of questions – I have prepared for Passover but have scant time to read your response(s.)
Background: threatened miscarriage (5-7 wks depending on dating, later if by LMP.) I have had three ‘missed miscarriages.’ I still have positive HPTs and symptoms of pregnancy and no cramping or bleeding despite a drop in b-HCG.
My current RE said the products of conception cannot be tested because it is too early in pregnancy. Should I seek a second opinion?
Thank you, K
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.
Please visit my new Blog on this very site, http://www.DrGeoffreySherIVF.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
•Ovarian Stimulation for IVF using GnRH Antagonists: Comparing the Agonist/Antagonist Conversion Protocol.(A/ACP) With the“Conventional” Antagonist Aproach
•IVF: Factors Affecting Egg/Embryo “competency” during Controlled Ovarian Stimulation(COS)
•IVF Failure and Implantation Dysfunction: The Role of Endometrial Thickness, Uterine Pathology and Immunologic Factors
•Vaginally Administered Viagra is Often a Highly Effective Treatment to Help Thicken a Thin Uterine Lining
•Why did my IVF Fail
•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)
•Natural Killer Cell Activation (NKa) and Immunologic Implantation Dysfunction in IVF: The Controversy!
•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 Fundamental Requirements For Achieving Optimal IVF Success
•
I invite you to arrange to have a Skype or an in-person consultation with me to discuss your case in detail. If you are interested, please contact Julie Dahan, at:
Email: Julied@sherivf.com
OR
Phone: 702-533-2691
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.
Geoff Sher
Thank you for your responses to my questions last week. I have applied for a one on one Skype consult re: my specific case but have general questions that may help my and others understanding. I will post them one at a time.
We have neither primary nor secondary subfertility. We have become pregnant every cycle excluding those with strict abstinence after the age of 36 (one live birth, one miscarriages and a threatened miscarriage as I type.) I am currently pregnant (at 42) but the outcome is certainly dire. My question: do couples who conceive easily have higher IVF success rates when staggering cycles and using PGS/NGS? Please guide me to references as I have found none. Thank you so much for your time and care. K
When Levent Keskintepe PhD and I first introduced PGS with full chromosomal karyotyping into the clinical IVF arena, we had no idea that it would so rapidly help fashion the field. Now PGS has become part of the IVF main stream. Using NGS and CGH technology (among other methods) embryos are fully karyotyped in one cycle when following a biopsy where one or more cells are removed for PGS testing they are vitrified (cryostored) while awaiting the results whereupon they are subsequently transferred (in a subsequent cycle) to the (i.e. Staggered-IVF). And when numerically chromosomally normal (euploid) eggs are transferred into a hospitable uterine environment the chance of a successful pregnancy increases significantly, the risk of miscarriage rate declines and the risk of a chromosomal defect such as Down syndrome is kept to a minimum. This has led to the approach gaining widespread use. Unfortunately (in my opinion it is now being “over-used”. In fact some programs virtually recommend PGS embryo testing to all their IVF patients. In my opinion this is wrong and fraught with often unforeseen circumstances. Bear in mind that PGS does NOT improve an embryo’s quality, it simply selects those embryos that are more likely to be “competent”. Egg/embryo “competency” remains primarily a function of age and the protocol used for controlled ovarian stimulation (COS). Consider the following:
1.In younger women (<35Y) with normal ovarian reserve, the selective transfer of 2 PGS-untested blastocysts (advanced embryos) will yield about the same chance of success (50-60%) as would the transfer of 1-2 euploid embryos. This is because 1:2 untested blastocysts are likely to be euploid anyway and each euploid blastocyst has about a 50-60% chance of resulting in a live birth. On the other hand in older women (36-45y) where depending on age , at best between 1:3 and 1:20 blastocysts are likely to be euploid PGS –based selection of embryos improves the chance of selecting the most ”competent” embryos for transfer. Thus, with the exception of younger women who have DOR those with “unexplained IVF failure” and women with RPL where embryo selection would improve success, PGS should in my opinion be largely confined to embryos derived from the eggs of women in their later 30’s and beyond. Staggered IVF with or without Embryo banking (stockpiling) is however an ideal method for blunting the effect of the biological clock and has particular merit in cases where the woman is older or has DOR and wants to avoid resorting to the use of donor eggs. In such cases, by selectively stockpiling and banking of PGS-euploid embryos over several cycles and then selectively transferring only them at a later date (Staggered IVF with Embryo Banking), it is now possible to improve IVF success rate per embryo transferred, reduce the miscarriage and chromosomal birth defect rate and provide women with an opportunity to have >1 baby over time.
2.Embryo mosaicism: Not all aneuploid embryos are doomed. There is a condition where a chromosomally normal embryo might subsequently become aneuploid during regular (mitotic) cell replication. Here, some of the embryos cells are chromosomally intact (euploid) while others are aneuploid. The condition is referred to as “mosaicism”. Mosaic embryos can autocorrect during subsequent development and produce normal offspring. This means that many aneuploid embryos should be banked and stored for possible future dispensation after full disclosure to the potential parents.
Geoff Sher