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.
Dear Dr. Sher,
Quite some time ago I read your article “Recurrent Unexplained IVF Failure with “Good Quality” Embryos” (dated April 30, 2018?) where you reported about a patient CJ (34 years old). Her NKa test (K-562 target cell test) result came back positive for activated killer cells. She was also found to have antiphospholipid antibodies (APA).
My case might be similar to hers. In my case three transfer attempts following an ICSI were not successful. Now a doctor for clinical transfusion medicine and immunodeficiency found that I have antiphospholipid antibodies but normal NK cells. Could you please help me and tell me what treatment could be successful for me ? I am already 42 years old.
Monika,
I definitely feel that we should talk.
Unless tests for immunologic implantation dysfunction (IID) are performed correctly and conducted by a one of the few reliable reproductive immunology reference laboratory in the United States, treatment will likely be unsuccessful. . In this regard it is most important that the right tests be ordered and that these be performed by a competent laboratory. There are in my opinion only a handful of reliable Reproductive Immunology Laboratories in the world and most are in the U.S.A. Also, it is my opinion that far too often, testing is inappropriate with the many redundant and incorrect tests being requested from and conducted by suboptimal laboratories. Finally for treatment to have the best chance of being successful, it is vital that the underlying type of IID (autoimmune IID versus alloimmune) be identified correctly and that the type, dosage, concentration and timing of treatments be carefully devised and implemented.
WHO SHOULD UNDERGO IID TESTING?
When it comes to who should be evaluated, the following conditions should in always raise a suspicion of an underlying IID, and trigger prompt testing:
•A diagnosis of endometriosis or the existence of symptoms suggestive of endometriosis (heavy/painful menstruation and pain with ovulation or with deep penetration during intercourse) I would however emphasize that a definitive diagnosis of endometriosis requires visualization of the lesions at laparoscopy or laparotomy)
•A personal or family history of autoimmune disease such as hyper/hypothyroidism (as those with elevated or depressed TSH blood levels, regardless of thyroid hormonal dysfunction), Lupus erythematosus, Rheumatoid arthritis, dermatomyositis, scleroderma etc.)
•“Unexplained” infertility
•Recurrent pregnancy loss (RPL)
•A history of having miscarried a conceptus that, upon testing of products of conception, was found to have a normal numerical chromosomal configuration (euploid).
•Unexplained IVF failure
• “Unexplained” intrauterine growth retardation due to placental insufficiency or late pregnancy loss of a chromosomally normal baby
What Parameters should be tested?
In my opinion, too many Reproductive Immunologists unnecessarily unload a barrage of costly IID tests on unsuspecting patients. In most cases the initial test should be for NK cell activation, and only if this is positive, is it necessary to expand the testing.
The parameters that require measurement include:
oFor Autoimmune Implantation Dysfunction: Autoimmune implantation dysfunction, most commonly presents with presumed “infertility” due to such early pregnancy losses that the woman did not even know she was pregnant in the first place. Sometimes there as an early miscarriage. Tests required are: a) blood levels of all IgA, IgG and IgM-related antiphospholipid antibodies (APA’s) directed against six or seven specific phospholipids, b) both antithyroid antibodies (antithyroid and antimicrosomal antibodies), c) a comprehensive reproductive immunophenotype (RIP) and, c) most importantly, assessment of Natural Killer (NK) cell activity (rather than concentration) by measuring by their killing, using the K-562 target cell test and/or uterine cytokine measurement. As far as the ideal environment for performing such tests, it is important to recognize that currently there are only about 5 or 6, Reproductive Immunology Reference Laboratories in the U.S capable of reliably analyzing the required elements with a sufficient degree of sensitivity and specificity (in my opinion).
oFor Alloimmune implantation Dysfunction: While alloimmune Implantation usually presents with a history of unexplained (usually repeated) miscarriages or secondary infertility (where the woman conceived initially and thereupon was either unable to conceive started having repeated miscarriages it can also present as “presumed” primary infertility. Alloimmune dysfunction is diagnosed by testing the blood of both the male and female partners for matching DQ alpha genes and NK/CTL activation. It is important to note that any DQ alpha match (partial or complete) will only result in IID when there is concomitant NK/CTL activation (see elsewhere on this blog).
How should results be interpreted?
Central to making a diagnosis of an immunologic implantation dysfunction is the appropriate interpretation of natural killer cell activity (NKa) .In this regard, one of the commonest and most serious errors, is to regard the blood concentration of natural killer cells as being significant. Rather it is the activity (toxicity) of NK cells that matters as mentioned. Then there is the interpretation of reported results. The most important consideration is the percentage of target cells “killed” in the “native state”. In most cases a level of >10% killing should be regarded with suspicion and >12% overtly abnormal. In my opinion, trying to interpret the effect of adding IVIG or Intralipid to the sample in order assess whether and to what degree the use of these products would have a therapeutic benefit is seriously flawed and of little benefit. Clinically relevant NK cell deactivation can only be significantly effected in vivo and takes more than a week following infusion to occur. Thus what happens in the laboratory by adding these products to the sample prior to K-562 target cell testing is in my opinion likely irrelevant.
There exists a pervasive but blatant misconception on the part of many, that the addition of Intralipid (IL) /immunoglobulin-G IVIG) can have an immediate down-regulatory effect on NK cell activity. This has established a demand that Reproductive Immunology Reference Laboratories report on NK cell activity before and following exposure to IVIG and/or IL. However, the fact is that activated “functional” NK cells (NKa) cannot be deactivated in the laboratory. Effective down-regulation of activated NK cells can only be adequately accomplished if their activated “progenitor/parental” NK cells are first down-regulated. Thereupon once these down-regulated “precursor” NK cells are exposed to progesterone, they will begin spawning normal and functional NK cells, which takes about 10-14 days. It follows that to assess for a therapeutic response to IVIG/IL therapy would require that the patient first be treated (10-14 days prior to embryo transfer) and thereupon, about 2 weeks later, be retested. While at 1st glance this might seem to be a reasonable approach, in reality it would be of little clinical benefit because even if blood were to be drawn 10 -14 days after IL/IVIG treatment it would require an additional 10 days to receive results from the laboratory, by which time it would be far too late to be of practical advantage.
Neither IVIG nor IL is capable of significantly suppressing already activated “functional NK cells”. For this to happen, the IL/IVIG would have to down-regulate progenitor (parent) NK cell” activity. Thus, it should be infused 10-14 several prior to ovulation or progesterone administration so that the down-regulated “progenitor/precursor” NK cells” can propagate a sufficient number of normally regulated “functional NK cell” to be present at the implantation site 7 days later. In addition, to be effective, IL/IVIG therapy needs to be combined with steroid (dexamethasone/prednisone/prednisolone) therapy to down-regulates (often) concomitantly activated T-cells.
I strongly recommend that you visit http://www.DrGeoffreySherIVF.com. Then go to my Blog and access the “search bar”. Type in the titles of any/all of the articles listed below, one by one. “Click” and you will immediately be taken to those you select. Please also take the time to post any questions or comments with the full expectation that I will (as always) respond promptly.
•The IVF Journey: The importance of “Planning the Trip” Before Taking the Ride”
•Controlled Ovarian Stimulation (COS) for IVF: Selecting the ideal protocol
•IVF: Factors Affecting Egg/Embryo “competency” during Controlled Ovarian Stimulation (COS)
•The Fundamental Requirements for Achieving Optimal IVF Success
•Use of GnRH Antagonists (Ganirelix/Cetrotide/Orgalutron) in IVF-Ovarian Stimulation Protocols.
•The Role of Immunologic Implantation Dysfunction (IID) & Infertility (IID): PART 1-Background
•Immunologic Implantation Dysfunction (IID) & Infertility (IID): PART 2- Making a Diagnosis
•Immunologic Dysfunction (IID) & Infertility (IID): PART 3-Treatment
•Thyroid autoantibodies and Immunologic Implantation Dysfunction (IID) Why did my IVF Fail
•Recurrent Pregnancy Loss (RPL): Why do I keep losing my PregnanciesGenetically Testing Embryos for IVF
•Staggered IVF
•Staggered IVF with PGS- Selection of “Competent” Embryos Greatly Enhances the Utility & Efficiency of IVF.
•Embryo Banking/Stockpiling: Slows the “Biological Clock” and offers a Selective Alternative to IVF-Egg Donation
•Preimplantation Genetic Testing (PGS) in IVF: It should be Used Selectively and NOT be Routine.
•IVF: Selecting the Best Quality Embryos to Transfer
•Preimplantation Genetic Sampling (PGS) Using: Next Generation Gene Sequencing (NGS): Method of Choice.
•PGS in IVF: Are Some Chromosomally abnormal Embryos Capable of Resulting in Normal Babies and Being Wrongly Discarded?
•Immunologic Implantation Dysfunction: Importance of Meticulous Evaluation and Strategic Management 🙁 Case Report)
•Intralipid and IVIG therapy: Understanding the Basis for its use in the Treatment of Immunologic Implantation Dysfunction (IID)
•Intralipid (IL) Administration in IVF: It’s Composition; how it Works; Administration; Side-effects; Reactions and Precautions
•Natural Killer Cell Activation (NKa) and Immunologic Implantation Dysfunction in IVF: The Controversy!
•Natural Killer Cell Activation (NKa) and Immunologic Implantation Dysfunction in IVF: The Controversy!
•Treating Out-of-State and Out-of-Country Patients at Sher-IVF in Las Vegas
•Should IVF Treatment Cycles be provided uninterrupted or be Conducted in 7-12 Pre-scheduled “Batches” per Year
•A personalized, stepwise approach to IVF
___________________________________________________________
ADDENDUM: PLEASE READ!!
INTRODUCING SHER FERTILITY SOLUTIONS (SFS)
Hitherto I have personally performed IVF- treatment and related procedures on patients who, elected to travel to Las Vegas to be managed by me. However, with the launching of Sher-Fertility Solutions (SFS) in April 2019, I have taken on a new and expanded role. Now, rather than having hands-on involvement I confine my services to providing hour-long online Skype consultations to an ever-growing number of patients (emanating from >40 countries), with complex Reproductive problems, who seek access to my input, advice and guidance. All Skype consultations are followed by a detailed written report that meticulously describes and explains my recommendations for treatment. All patients are encouraged to share this report with their personal treating doctor(s), with whom [subject to consent and a request from their doctor] I will, gladly discuss their case with the “treating Physician”.
Through SFS I am now able to conveniently provide those who because of geography, convenience and cost, prefer to be treated at home or elsewhere by their chosen Infertility Physician.
“I wish to emphasize to all patients with whom I consult, that in the final analyses, when it comes to management, strategy, protocol and implementation of treatment, my advice and recommendations are always superseded by that of the hands-on treating Physician”.
Anyone wishing to schedule a Skype consultation with me, can do so by: Calling my concierge (Patti Converse) at 1-800-780-7437 (in the U.S.A or Canada) or 702-533-2691, for an appointment. Patients can also enroll online on my website, http://www.SherIVF.com, or email Patti at concierge@SherIVF.com .
I was very recently greatly honored in receiving an award by the prestigious; International Association of Top Professionals (IAOTP). For more information, go to the press release on my website, http://www.sherIVF.com .
PLEASE HELP SPREAD THE WORD ABOUT SFS!
Geoff Sher
Dear Dr Sher, I am 31 years old, my husband is 28 years old. He had very low sperm parameters but then underwent varicocele b/l surgery, after 3 months of which, his count is normal. Morpho 12%, count 50 million, motility 55%. Is it still recommended that we go for IVF/ICSI like we did PRIOR to improvement in semen parameters ( 1 failed ivf/Isci cycle before varicocele surgery). Or can we try naturally or with IUI now?
Also, In case we go for IVF, what are our overall chances, Sir? My AMH is 2.3, during egg retrieval I got around 11 eggs picked, endometrial lining was 8.1mm. Also my tube has loculated spill on one side. I have 28 day cycle. We are confused with the varying opinions and hence look forward to your expert guidance. Best.
If you have no definable cause for infertility and your husband’s sperm parameters are as stated, then given your young age, I would opt for IUI. However, there could be a hitherto undiagnosed cause for your infertility, that might mandate IVF. I suggest we talk.
Intrauterine insemination (IUI), the injection of sperm into the uterus by means of a catheter directed through the cervix, has been practiced for many years. The premise of this procedure is that sperm can reach and fertilize the egg more easily if placed directly into the uterine cavity. IUI is a procedure that bypasses the cervix and places specially prepared sperm into a woman’s uterus around the time of natural or induced ovulation. The suggested advantage of IUI is that it shortens the path that sperm would normally take to a woman’s fallopian tubes.
In the early ‘60s, physicians were injecting small quantities of raw, untreated semen, (sperm plus the seminal plasma) directly into the uterus at the time of expected ovulation. However, when more than 0.2 ml of semen was injected in to the uterus, serious and sometimes life endangering shock-like reactions often occurred. It was subsequently identified that the reason for such reactions related to the presence of prostaglandins within the seminal plasma. This led to the practice of injecting small amounts (less than 0.2 ml) of raw semen. However, the pregnancy rates were dismal and side effects, such as severe cramping and infection were rampant.
Soon after establishing the Northern Nevada Fertility Center in Reno in 1982 (the Nation’s first private in vitro fertilization (IVF program), we began to recognize the potential advantage of washing and centrifuging raw semen, so as to separate sperm from the seminal fluid, and thereby remove prostaglandins that cause most of the problems. We subsequently introduced and, thereupon, became the first to publish on intrauterine insemination (IUI) in the Journal, Fertility and Sterility (April 1984).
Indications for Intrauterine Insemination (IUI)
•Artificial insemination using frozen (donor) sperm: The recognition of HIV infection as a sexually transmitted disease, coupled with the fact that the virus is present in semen months before it can be detected in the blood, mandates that all donors have their semen cryopreserved (frozen) and stored for at least six months, whereupon, they be re-tested for HIV infection. Only upon confirmation of a negative test should the cryopreserved semen specimen be thawed and used for insemination. Since cryopreservation inevitably reduces sperm motility and function, it is not adequate to simply thaw the frozen specimen and then inseminate the raw semen into the vagina. Rather, the semen specimen should be processed for IUI. Provided that the recipient is ovulating normally, there is no need to administer fertility drugs, such as Clomiphene, Pergonal, etc.
•Artificial insemination with partner’s sperm: In cases of sexual dysfunction (impotence, retrograde ejaculation, etc.) or timing issues, partner’s sperm may need to be collected and processed in preparation of IUI.
•Cervical mucus hostility: Sometimes the cervical mucus acts as a barrier to the activation and passage of sperm as it passes through the cervical canal. Such hostility may be due to poor physical qualities of the mucus, cervical infection, or the presence of antisperm antibodies. In all but the latter situations, IUI can readily be performed during natural cycles, unless the woman has ovulation dysfunction. However, when infertility results from the presence of antibodies in the cervical mucus, IUI will likely be ineffectual and should be replaced by in vitro fertilization (IV).
•Absent or dysfunctional ovulation: In some cases where the woman requires the use of fertility drugs to induce normal ovulation, the concomitant performance of IUI might improve pregnancy rates.
Selecting the Fertility Drugs for Intrauterine Insemination (IUI)
Clomiphene citrate (Serophene, Clomid): Clomiphene citrate is taken orally for 5 days starting on day 2 to 5 of the menstrual cycle. Ovulation will usually occur 10 days later. In some cases, hCG is used to trigger the ovulation but this is often unnecessary. Clomiphene is a relatively inexpensive and safe method for inducing ovulation and this is why it is so commonly prescribed to women undergoing IUI. However, women receiving clomiphene have about a one third lower pregnancy rate per cycle than is the case using injectible fertility drugs. but it there are draw-backs. Here are a few reasons why this is so:
1)Clomiphene citrate is an anti-estrogen. .Ordinarily normally ovulating women (without exposure to clomiphene) produce a single dominant follicle which produces enough estrogen to promote optimal cervical mucous production and an adequate endometrial lining (>9mm) However, with clomiphene is used to induce ovulation, its anti-estrogenic effect blunts this response. In fact on clomiphene,it requires much more estrogen to override this effect such that unless at least 3 large follicles develop so as to allow the blood estradiol levels to rise above 400pg/ml, cervical mucus production and endometrial development will usually be insufficient to allow a healthy pregnancy to occur. Younger women with normal ovarian reserve (Day-3 FSH of <9miu/ml) will usually produce >3 follicles where as women over 40 years of age and those (regardless of age) with diminished ovarian reserve will rarely do so and thus are very unlikely to achieve viable pregnancies on clomiphene
2)Clomiphene induction of ovulation is associated with a 15-20% chance of a condition called luteinized unruptured follicle (LUF) syndrome where the hormonal changes that precede and accompany and follow ovulation (including a rise in blood progesterone level) occur but this happens without ovulation occurring .LUF syndrome thus leads to the erroneous conclusion that an egg has been released when, in fact, it remains “trapped” in the ovarian follicle.
3)More than 3 consecutive (back to back) of clomiphene will result in a very significant increase in the anti-estrogen effects (referred to in 1&2 above), such that unless a break of at least 1 full menstrual cycle is taken, the likelihood of a viable pregnancy declines to less than 10%, regardless of the woman’s age or her ovarian reserve.
4)Increased production of Luteinizing Hormone: Clomiphene causes the pituitary gland to produce increased amounts of FSH and LH. FSH promotes follicle growth development while excess LH causes the ovary to produce male hormones such as testosterone. While a little testosterone is indispensable to follicle and egg development, too much testosterone can have the reverse effect and harm egg development. This effect is even more deleterious in women with diminished ovarian reserve (elevated FSH levels) and those over 40 whose ovaries tend to produce more testosterone-like hormones.
The following additional factors must be considered when it comes to the use of Clomiphene:
1)It is best not being prescribed for more than three consecutive months in a row to anyone and certainly not without taking a full cycle break before restarting a fourth cycle of treatment. The reason is that after the 3-4 consecutive months of clomiphene therapy, the anti-estrogenic properties are compounded to the effect of virtually converting it to an anti-fertility drug. This explains why >80% of successful clomiphene pregnancies occur within the first 3 months of treatment, and why the vast majority of clomiphene pregnancies that occur after >3 consecutive (back-to-back) cycles of treatment are lost (usually due to early miscarriages).
2)Clomiphene should not be used in women that have diminished ovarian reserve (e.g. women with elevated FSH levels) or in women over 40 years of age.
The good news is that upon discontinuation of Clomiphene for 4-6 weeks, adverse effects disappear, leaving the slate clean.
The real benefit of clomiphene lies in its oral route of administration, low incidence of side effects, and its low cost. The birth rate per clomiphene IUI is about 7-10% per cycle of treatment (about 1/3 lower than when injectible fertility drugs are used.
Letrozole(Femara): Letrozole, like clomiphene is an oral agent induces ovulation that causes the pituitary gland to release large amounts of FSH as well as LH. The advantage that Letrozole has over clomiphene is that unlike the latter, it is NOT anti-estrogenic and thus does not compromise development of the uterine lining or adversely affect the production of cervical mucus. However as is the case with clomiphene, Letrozole causes increased LH release that can lead to overproduction of male hormones (e.g. testosterone) by the ovaries with potentially adverse effect on egg/embryo quality.
Thus while Letrozole does have potential advantages over clomiphene, the exaggerated LH-induced testosterone effect, especially in women over 40 years of age and/or those with evidence of diminished ovarian reserve limits its value.
Gonadotropins (Menopur, Gonal-f, Folistim and Puregon:) Women with absent or abnormal ovulation who require fertility drugs in preparation for IUI should receive gonadotropins. Granted, these agents are more expensive than clomiphene, but they have no anti-estrogenic properties.
The birth rate with gonadotropin IUI in women under 35 years of age (in the absence of male infertility, where it is much lower) is about 10-15%. However, success is affected by, and contingent upon, the procedure being performed (1) for the correct indications, (2) avoiding the performance of IUI when contraindications exist (see below) and, (3) where the woman is ovulating normally on her own. Success rates decrease as a woman’s age advances. In women 35-40 years of age the birth rate is 5-10% per cycle and for over 40 years, the birth rate per cycle is under 2%, declining to less than 1% after age 43.
Relative Contraindications to Intrauterine Insemination (IUI)
Advancing age: A woman’s natural ability to conceive declines with age starting after age 30. It falls more rapidly after age 35 and then, precipitously so after 40. The main reason for this is that the percentage of eggs that become chromosomally abnormal (aneuploid) through “wear and tear” increases as she gets older, such that by age 40 an ovulated egg is probably 3 times less likely to be able to propagate a viable pregnancy than at age 30. This explains the fact that under 35, the normally ovulating woman who receives injectible fertility drugs to induce ovulation has about a 10-12% chance of having a baby. In comparison, after age 40, the same woman would have about a 2% chance. For this reason alone, IUI is best suited to women under 35 and, in my opinion, should NOT be undertaken after age 40. Ages between 35 and 40 represent a “gray area.”
Significant Male Infertility: Contrary to popular belief, the performance of IUI in cases of male infertility does not improve success rates over regular and well-timed intercourse alone. In vitro fertilization with intracytoplasmic sperm injection (IVF/ICSI) is the only method to optimize pregnancy rates in association with male refractory infertility.
Tubal damage
1.Post-Pelvic Inflammatory Disease (PID): It is very important to understand that Fallopian tubes are not mere “pipes” through which sperm, egg and embryo must pass to achieve an intrauterine pregnancy. They are vital and sophisticated organs that serve intricate functions in the reproductive process. They transport sperm in the direction of the ovary, while at the same time, the fimbriae (petal-like extrusions at the end of the tube) apply themselves to the area of the ovary from which the egg is ovulating in order to pick up the extruding egg, and carry it back down the tube towards the uterus. About one third of the way back, the egg encounters the sperm and fertilization occurs. Thereupon, the resulting embryo is transported to the uterine cavity where it hopefully will implant.
PID, the commonest cause of damaged Fallopian tubes will, unless it is diagnosed and effectively treated very early on, inevitably and permanently disrupt the sophisticated function and continuity of the inner lining of both Fallopian tubes. In more severe cases, the intricate muscular arrangement of the tubal wall is also damaged, compromising the time-sensitive and programmed migration of sperm, egg and embryo. In advanced cases of PID, the fimbria fuse, thus compromising egg pick-up, and ultimately blocking the tube(s) completely.
PID almost always affects both Fallopian tubes. Indeed, one tube might be more damaged than the other, but both will be affected to a greater or lesser degree. That is why, even if one tube remains or is surgically rendered patent, the problem of markedly reduced fertility and the increased risk of a subsequent tubal pregnancy remains an ever present risk and reality. Thus, the use of fertility drugs to induce ovulation, or the use of microsurgery to open Fallopian tubes and free surrounding adhesions are often not curative of infertility. Furthermore, in cases where a pregnancy follows, the result is often a tubal (ectopic) gestation. This also serves to explain the fact that the intrauterine pregnancy rate following ovulation induction (with or without concomitant IUI) is likely to be to be at least 10 times lower in women with PID, and why, when a pregnancy does ensue, it is 10 times more likely to be a tubal (ectopic).
Thus, in women who have had PID, IVF is the only way to safely bypass the “damaged plumbing” and initiate a viable intrauterine pregnancy.
2.Post-Tubal Ligation. In large part, the same holds true following successful reconnection of previously ligated (tied) Fallopian tubes. The reason is that even with successful surgical reestablishment of tubal patency, there is always a degree of shortening of the tube(s) or a degree of damage due to surgical scarring of the inner lining of the tube(s). Even when tubes are normal, the birth rate per IUI cycle is about 10%, and following any form of tubal damage (PID or surgically-induced) the success is 5-10 times lower per IUI cycle (i.e. 1%-2%). Hence, IUI can hardly be justified in such cases, and IVF becomes the only effective and viable option.
Endometriosis:
While the exact cause of endometriosis remains an enigma, it is now apparent that immunologic dysfunction is a significant feature of this disease, and that a toxic environment exists in the pelvis (surrounding the tubes and ovaries) in patients with this condition. As a consequence, ovulation – whether spontaneous or induced by fertility drugs – commits the egg to pass through a toxic pelvic environment in order to reach the sperm waiting in the fallopian tube. This significantly reduces the egg’s fertilization potential. Furthermore, once the fertilized egg reaches the uterus, immunologic factors associated with endometriosis increase the risk of the embryo being rejected before pregnancy can be diagnosed. Such women may experience repeated “mini-miscarriages.”
In spite of these anti-fertility influences, many women with mild endometriosis do in fact conceive on their own, or following ovarian stimulation with fertility drugs. However, for reasons already referred to, the chances of conception are significantly reduced. And if they are ovulating normally on their own, the addition of fertility drugs will afford no additional benefit. Simply put, women in their late 20’s to early 30’s who have the time can anticipate about a 40% chance of conceiving on their own within two or three years (contingent upon their ovulating normally and having a fertile male partner). The occurrence of pregnancy in the latter cases occurs in spite of, rather than due to, such treatment. Such women may consider deferring any invasive treatments in favor of a “wait-and-see” approach. Conversely, women over the age of 35 whose egg quality is inevitably on the decline, IVF offers the only rational approach.
Fertility Drugs and Multiple Births
Normally ovulating women usually develop a number of follicles (fluid filled spaces within the ovary(ies) that contain eggs and produce estrogen) during the first week of the menstrual cycle. All but one (and sometimes two) of the follicles fail to develop to the point of being eligible for ovulation. The process is known as Selection. It is important to recognize that in all normally ovulating women, the one or two follicles selected to ovulate will inevitably be larger than the remaining follicles, regardless of whether the woman is receiving fertility agents such as Clomiphene or gonadotropins (Follistim/Gonal-F/Puregon/Fostimon/Menopur, etc). Simply put, one or two follicles will always show enhanced development over the others, and as soon as these selected follicles ovulate, all the remaining follicles are rendered incapable of following suit. As a result, normally ovulating women no not have a greater incidence of high order multiple pregnancies. In contrast, women who do not ovulate at all, and those who ovulate irregularly or dysfunctional do not have the ability to select one or two dominant follicles for ovulation. As such, following the administration of fertility drugs for ovarian stimulation, numerous follicles may develop at the same rate, and several eggs can be ovulated simultaneously. This translates into a greater chance of pregnancy, but also a greater chance of multiple pregnancies. It is interesting that almost all reported cases of high order multiple pregnancies (greater than twins) following the use of fertility drugs have occurred in women who do not ovulate normally on their own.
It follows that only those women with absent or abnormal ovulation are at-risk for high order multiple pregnancies. They, therefore, need to be counseled regarding the consequences of premature birth and the availability of selective pregnancy reduction towards the end of the third month of pregnancy. Another alternative is to avoid the issue completely by choosing in vitro fertilization (IVF), where the number of potential babies can be limited by the number of embryos transferred to the uterus.
It is indeed unfortunate that fertility treatment has become so regimented that most patients find themselves being ushered through a scripted treatment process. As an example, clomiphene, though favored for its convenience and low cost, does NOT yield the same success as IUI with gonadotropin stimulation. In fact the per-cycle success rate of IUI using clomiphene is about 30% less. Also, women with endometriosis (regardless of severity) have much lower success with IUI (see above). Women over age 40 have such a low success with IUI that they cannot afford the time wasted in the process. Such women need IVF.
For the majority of couples who require an individualized strategic plan of action at an early stage, such an approach is emotionally, physically, and financially draining, leaving them both suspicious and critical of the intent of the medical profession.
The introduction of inexpensive Micro-IVF changes the landscape. In fact, the success rate is three times higher than with IUI. This plus the low the relatively low cost of Micro-IVF (as compared with conventional IVF) is a major advantage of the approach.
ADDENDUM: PLEASE READ!!
INTRODUCING SHER FERTILITY SOLUTIONS (SFS)
Hitherto I have personally performed IVF- treatment and related procedures on patients who, elected to travel to Las Vegas to be managed by me. However, with the launching of Sher-Fertility Solutions (SFS) in April 2019, I have taken on a new and expanded role. Now, rather than having hands-on involvement I confine my services to providing hour-long online Skype consultations to an ever-growing number of patients (emanating from >40 countries), with complex Reproductive problems, who seek access to my input, advice and guidance. All Skype consultations are followed by a detailed written report that meticulously describes and explains my recommendations for treatment. All patients are encouraged to share this report with their personal treating doctor(s), with whom [subject to consent and a request from their doctor] I will, gladly discuss their case with the “treating Physician”.
Through SFS I am now able to conveniently provide those who because of geography, convenience and cost, prefer to be treated at home or elsewhere by their chosen Infertility Physician.
“I wish to emphasize to all patients with whom I consult, that in the final analyses, when it comes to management, strategy, protocol and implementation of treatment, my advice and recommendations are always superseded by that of the hands-on treating Physician”.
Anyone wishing to schedule a Skype consultation with me, can do so by: Calling my concierge (Patti Converse) at 1-800-780-7437 (in the U.S.A or Canada) or 702-533-2691, for an appointment. Patients can also enroll online on my website, http://www.SherIVF.com, or email Patti at concierge@SherIVF.com .
I was very recently greatly honored in receiving an award by the prestigious; International Association of Top Professionals (IAOTP). For more information, go to the press release on my website, http://www.sherIVF.com .
PLEASE HELP SPREAD THE WORD ABOUT SFS!
Geoff Sher
Hello doctor
We are using an egg donor. I learned the donor recently traveled to Mexico. Is it unsafe to use her?
I am not positive, but I believe that that this could pose a problem. Check with your RE’d officer.
Geoff Sher
Hi Dr. Sher
Most likely, I do not have PCOS and definitively, I do not have problems with my sugar amount.
Still, my clinic puts me almost 3 months before embryo transfer on 3 pills a day of Metformin.
Is there something beneficial in doing so? Is there something harmful in doing so?
Thanks
It probably wont do harm, but it is my policy not to prescribe Metformin without documented evidence of hyperinsulinism.
Geoff Sher
Dear Dr Sher
I have done multiple banking cycles and PGS testing. A few of the embryos tested as inconclusive and it was recommended to re-biopsy. Additionally I have two frozen embryos from a previous cycle that are untested. In your opinion is it safe to thaw frozen embryos, biopsy and then freeze again? Especially considering the limitations of PGS my inclination is to transfer without testing/retesting because I do not want to risk losing the embryos in the process of thawing, re-freezing and thawing again. Thank you!
Pregnancies are reported with 2ndary testing, but in my opinion, it is very stressful on the embryos and I would not re-test.
Good luck!
Geoff sher