– Geoffrey Sher, MD
Fill in the following information and we’ll get back to you.
Name: Kathryn T
Hi there,
I am 36 years old with 2 children already my husband is 39.
We have been trying to conceive number 3 for close to 2 years and have experienced miscarriage & struggle conceiving.
My AMH is 6.5. Recently we have found out that my husband has antisperm antibodies at 56%.
We have been recommended IVF with ICSI however with a large cost it is a hard decision.
Would IUI still be worth trying?
Or is this a waste of money with antisperm?
With sperm antibodies, IUI is really not a tangible option. You need IVF/ICSI.
Antisperm antibodies (ASA) are immunoglobulins that attach to sperm. They are most commonly encountered in semen, blood, cervical mucous and follicular fluid. Not all ASA bind to sperm. However, those that do so can inhibiting fertilization. Methods used to detect for the presence of SAs in blood, in the seminal plasma of the ejaculate or in the cervical mucus only measure those immunoglobulins that bind to sperm components.
ASAs are related to the stimulation of sperm antigen. Detection of ASA requires access to standard sperm antigens that are associated with fertilization. An ideal sperm antigen should be sperm specific, accessible to the antibody and play a key role in fertilization..
In about 1-4% of infertility cases the presence of antisperm antibodies (ASA) in the male or female appear to be the cause. While the presence of ASA reduces both male and fertility significantly, it does not necessarily always prevent conception altogether. Rather, the effects are graduated; i.e., the larger the immunologic response (concentration of antibodies), the less likely it is that a pregnancy will occur and when the blood level rises above 40%, natural conception is highly unlikely to occur.
Like any other kind of antibody manufactured by the body, sperm antibodies are formed in response to antigens. These antigens are proteins, which appear on the outer sperm membranes as the young sperm cells, develop within the male testes. In the man’s own body, his sperm are regarded as foreign invading proteins and as such would normally be targeted for attack However, under normal conditions, direct contact between the man’s blood and sperm is prevented by a cellular structure in the testes called the blood/testis barrier. This barrier is formed by so-called, Sertoli cells, which abut very closely against each other, forming tight junctions that separate the developing sperm cells from the blood and prevent immunologic stimulation. However, the blood/ testis barrier can be broken by physical or chemical injury or by infection. When this barrier is breached, sperm antigens escape from their immunologically protected environment and come in direct contact with blood elements that launch an immunologic attack.
Once sperm and blood come in contact, whether in the male or female, specific antibodies are produced against them by specialized blood cells call T- and B-lymphocytes. The three main types of sperm antibodies produced are Immunoglobulin G (IgG), Immunoglobulin A (IgA) and Immunoglobulin M (IgM). These antibodies bind to the proteins (antigens) on the sperm head, midpiece or tail. The antibodies formed may be of the circulatory type (in the blood serum) or secretory type (in the tissue). This is important because high levels of antibodies in the blood serum do not invariably mean that the antibodies will find their way to the semen where they can affect the sperm. For example, the concentration of IgG is much lower in secretions of the reproductive tract that it is in the blood. Conversely, the local level of IgA is higher in the reproductive secretions than in the blood. This is an important point, which we will return to later.
Once sperm antibodies have formed, they can affect sperm in several different ways. Some antibodies will cause sperm to stick together or agglutinate. Agglutinated sperm clump together in dense masses and thus are unable to migrate through the cervix into the uterus. Other antibodies mark the sperm for attack by Natural killer (NK) cells of the body’s immune system (ie; opsonizing antibodies). Some antibodies cause reactions between the sperm membrane and the cervical mucus preventing the sperm from swimming through the cervix (ie; immobilizing antibodies). Antibodies can also block the sperm’s ability to bind to the zona pellucida of the egg, a prerequisite for fertilization (ie; blocking antibodies). Finally, there is recent evidence that the fertilized egg shares some of the same antigens that are found on the sperm. It is possible that sperm antibodies present in the mother can react with the early embryo, resulting in its destruction by phagocytic (ie; phagocytic antibodies) cells.
In my opinion, ASA tests are best performed on blood. There are a number of diagnostic tests available to detect the presence of sperm antibodies. There are several methods for the diagnosis These tests are performed by flow cytometry and the ELISA (enzyme-linked immunoabsorbent assay), the Franklin-Dukes sperm agglutination assay or the Immunobead Binding Test (IBT).the indirect immunofluorescence (IIF) assay, to name a few. My preference is the IBT.
In the male, IgA and IgG are found in the semen although there is controversy as to whether they originate locally (secreted by testicular cells) or cross over from the circulation. Antibodies of the IgM class are not found in semen.
Like the source of some antibodies, the question of the critical levels of sperm antibodies is also hotly debated among clinicians. There seems to be general agreement that blood levels above 30% by the IBT are associated with significant fertility problems.
ADDITIONAL INFORMATION:
I am attaching online links to two E-books which I recently co-authored with my partner at SFS-NY (Drew Tortoriello MD)……. for your reading pleasure:
1.From In Vitro Fertilization to Family: A Journey with Sher Fertility Solutions (SFS) “
https://sherfertilitysolutions.com/sher-fertility-solutions-ebook.pdf
https://drive.google.com/file/d/1iYKz-EkAjMqwMa1ZcufIloRdxnAfDH8L/view
Studiers have shown that pregnancy is highly unlikely following natural intercourse or intrauterine insemination when either the woman or the man harbors significant antisperm antibodies.
Attempts have to try and remove antibodies from sperm by allowing the sperm to swim through a column of beads are by and large unsuccessful. And, while there have been isolated reports that administration of corticosteroids (eg; prednisone) will temporarily suppress antibody production pregnancy rates are poor. Besides, corticosteroid therapy carries with it the risk of significant side, some of which (although infrequent) can be serious. As an example, in the man spontaneous fractures (especially of the neck of the femur) have been reported in 2 % of cases. I do not recommend this treatment.
In Vitro Fertilization (IVF) with intracytoplasmic Sperm injection (ICSI) is the best option. Here each egg is injected with a single sperm and whether there are antibodies attached to the outer surface of the sperm becomes irrelevant.. In fact, pregnancy and birth rates are the same as in cases where IVF is performed for reasons other than male factor infertility. IVF/ICSI success rates are also .not unaffected by the concentration of antisperm antibodies.
Name: Angharad B
Hello, I have had 3 rounds of ivf and twice had 6/7 follicles and only 3 eggs. Now I had 9 follicles and 1 egg. I am 37 and AMH around 7 pmol. I have been having several false peaks on my LH strips the past few months, as well as a LOT of egg white mucus sometimes and at the start of this ivf. Are these signs of high LH? What would be a possible suggested protocol for next round? Thanks so much fot any information. Kind regards, Angharad
Frequently, when following vigorous and often repeated flushing of follicles at egg retrieval they fail to yield eggs, it is ascribed to “Empty Follicle Syndrome.” This is a gross misnomer, because all follicles contain eggs. So why were no eggs retrieved from the follicles? Most likely it was because they would/could not yield the eggs they harbored.
This situation is most commonly seen in older women, women who have severely diminished ovarian reserve, and in women with polycystic ovarian syndrome (PCOS). In my opinion it is often preventable when an optimal, individualized and strategic protocol for controlled ovarian stimulation (COS) is employed and the correct timing and dosage is applied to the “hCG trigger shot.”
Normally, following optimal ovarian stimulation, the hCG “trigger shot” is given for the purpose of it triggering meiosis (reproductive division) that is intended to halve the number of chromosomes from 46 to 23 within 32-36 hours. The hCG trigger also enables the egg to signal the “cumulus cells” that bind it firmly to the inner wall of the follicle (through enzymatic activity), to loosen or disperse, so that the egg can detach and readily be captured at egg retrieval (ER).
Ordinarily, normal eggs (and even those with only one or two chromosomal irregularities) will readily detach and be captured with the very first attempt to empty a follicle. Eggs that have several chromosomal numerical abnormalities (i.e., are “complex aneuploid”) are often unable to facilitate this process. This explains why when the egg is complex aneuploid, its follicle will not yield an egg…and why, when it requires repeated flushing of a follicle to harvest an egg, it is highly suggestive of it being aneuploid and thus “incompetent” (i.e., incapable of subsequently propagating a normal embryo).
Older women, women with diminished ovarian reserve, and those with polycystic ovarian syndrome, tend to have more biologically active LH in circulation. LH causes production of male hormone (androgens, predominantly testosterone), by ovarian connective tissue (stroma/theca). A little testosterone is needed for optimal follicle development and for FSH-induced ovogenesis (egg development). Too much LH activity compromises the latter, and eggs so affected are far more likely to be aneuploid following meiosis.
Women with the above conditions have increased LH activity and are thus more likely to produce excessive ovarian testosterone. It follows that sustained, premature elevations in LH or premature luteinization (often referred to as a “premature LH surge”) will prejudice egg development. Such compromised eggs are much more likely to end up being complex aneuploid following the administration of the hCG trigger, leading to fruitless attempts at retrieval and the so called “empty follicle syndrome.”
The developing eggs of women who have increased LH activity (older women, women with diminished ovarian reserve, and those with PCOS) are inordinately vulnerable to the effects of protracted exposure to LH-induced ovarian testosterone. Because of this, the administration of medications that provoke further pituitary LH release (e.g., clomiphene and Letrozole), drugs that contain LH or hCG (e.g., Menopur), or protocols of ovarian stimulation that provoke increased exposure to the woman’s own pituitary LH (e.g., “flare-agonist protocols”) and the use of “late pituitary blockade” (antagonist) protocols can be prejudicial.
The importance of individualizing COS protocol selection, precision with regard to the dosage and type of hCG trigger used, and the timing of its administration in such cases cannot be overstated. The ideal dosage of urinary-derived hCG (hCG-u) such as Novarel, Pregnyl and Profasi is 10,000U. When recombinant DNA-derived hCG (hCG-r) such as Ovidrel is used, the optimal dosage is 500mcg. A lower dosage of hCG can, by compromising meiosis, increase the risk of egg aneuploidy, and thus of IVF outcome.
There is in my opinion no such condition as “Empty Follicle Syndrome.” All follicles contain eggs. Failure to access those eggs at ER can often be a result of the protocol used for controlled ovarian stimulation.
_______________________________________
ADDITIONAL INFORMATION:
I am attaching online links to two E-books which I recently co-authored with my partner at SFS-NY (Drew Tortoriello MD)……. for your reading pleasure:
1.From In Vitro Fertilization to Family: A Journey with Sher Fertility Solutions (SFS) “
https://sherfertilitysolutions.com/sher-fertility-solutions-ebook.pdf
https://drive.google.com/file/d/1iYKz-EkAjMqwMa1ZcufIloRdxnAfDH8L/view
Name: Marcella J
Hello Dr,
I have pcos and I am 40 years old. I have an 8 year old and over the years, I’ve been through 7 rounds of timed intercourse with ovidrel with no success. My doctor is recommending a round of IUI next with injectibles (rekovelle in lower doses) before moving onto a round or 2 of ivf.
My mom is a breast cancer survivor (estrogen positive) and having pcos, myself I’m concerned about the use of fertility drugs (ovidrel and other injectibles) and the risk of developing ovarian cancer. As mentioned I’ve taken ovidrel almost 8 times and will be stimulated further with stronger meds for IUI and ivf in the months to come. Can you please shed some light on this? I have been reading multiple studies some saying there is a risk and others saying there is no/minimal risk.
Ever since January 1993 when a study was reported by researchers at Stanford University suggesting that the use of fertility agents increased the risk of ovarian cancer, there has been tremendous concern and anxiety among women who use fertility drugs. At first the findings seemed well founded because intuitively it made biological sense that fertility drugs might promote cancer because they increase the number of ovulations a woman has. And so the studies received wide public attention. It subsequently turned out that this study which was based on, data compiled from 12 retrospective studies on ovarian cancer patients done in the late seventies and early eighties was seriously flawed for the following reasons:
Most important is the fact that several large prospective studies have now refuted the existence of a link between the use of gonadotropins and ovarian cancer. On the other hand, there does appear to be an association between ovarian cancer and certain causes of infertility itself, such as endometriosis.
While the case is still out with regard to whether or not in humans the prolonged and repeated use of clomiphene citrate increases the risk of ovarian cancer, when it comes to the use of gonadotropins for controlled ovarian stimulation (COS) women can in my opinion, breathe easy.
ADDITIONAL INFORMATION:
I am attaching online links to two E-books which I recently co-authored with my partner at SFS-NY (Drew Tortoriello MD)……. for your reading pleasure:
1.From In Vitro Fertilization to Family: A Journey with Sher Fertility Solutions (SFS) “
https://sherfertilitysolutions.com/sher-fertility-solutions-ebook.pdf
https://drive.google.com/file/d/1iYKz-EkAjMqwMa1ZcufIloRdxnAfDH8L/view
………………………………………………………………..
Name: Christie C
Is there a bmi limit for IVF treatment?
Not really!
ADDITIONAL INFORMATION:
I am attaching online links to two E-books which I recently co-authored with my partner at SFS-NY (Drew Tortoriello MD)……. for your reading pleasure:
1.From In Vitro Fertilization to Family: A Journey with Sher Fertility Solutions (SFS) “
https://sherfertilitysolutions.com/sher-fertility-solutions-ebook.pdf
https://drive.google.com/file/d/1iYKz-EkAjMqwMa1ZcufIloRdxnAfDH8L/view
………………………………………………………………..
Name: Audrey V
Hello! Do you use BMI as a metric for prescribing fertility inducing medication (Clomid/letrozole)? If so, what is the maximum BMI allowed? Thank you!
No! By and large, I do not!
Geoff Sher
___________________________________________________________
ADDITIONAL INFORMATION:
I am attaching online links to two E-books which I recently co-authored with my partner at SFS-NY (Drew Tortoriello MD)……. for your reading pleasure:
1.From In Vitro Fertilization to Family: A Journey with Sher Fertility Solutions (SFS) “
https://sherfertilitysolutions.com/sher-fertility-solutions-ebook.pdf
https://drive.google.com/file/d/1iYKz-EkAjMqwMa1ZcufIloRdxnAfDH8L/view
………………………………………………………………..
Name: Liza A
I have short (25 day) cycles with early recruitment of follicles, and a history of lead follicles and asynchronous growth during previous IVF.
My dr instructed me to take 21 days BC before beginning my IVF cycle with 3 days Decapeptyl, followed by Gonal F from 3rd day onwards. Due to a miscommunication, I only started BC on day 6 of my cycle, instead of day 1. I was told this was ok, but I am concerned I have messed up my cycle.
Could you please advise if I am more at risk of developing dominant follicles due to starting the BC late?
Thank you for your insight.
I do not think that starting the BCP on Day-6will have any adverse effects on your treatment.
One often hears the expressed opinion that the BCP suppresses response to ovarian stimulation. This is not the case, provided that the BCP is overlapped with administration of an agonist (e.g. Lupron, Buserelin, Superfact) for several days leading up to the start of menstruation and the initiation of ovarian stimulation cycle with gonadotropin drugs. If the latter precaution is not taken, and the cycle of stimulation is initiated coming directly off the BCP the response will often be blunted and subsequent egg quality could be adversely affected. The explanation for this is that in natural (unstimulated) as well as in cycles stimulated with fertility drugs, the ability of follicles to properly respond to FSH stimulation is dependent on their having developed FSH-responsive receptors . Pre-antral follicles (PAF) do not have such primed FSH receptors and thus cannot respond properly to FSH stimulation with gonadotropins. The acquisition of FSH receptor responsivity requires that the pre-antral follicles be exposed to FSH, for a number of days (5-7) during which time they attain “FSH-responsivity” and are now known as antral follicles (AF). These AF’s are now able to respond properly to stimulation with administered FSH-gonadotropins. In regular menstrual cycles, the rising FSH output from the pituitary gland insures that PAFs convert tor AF’s. The BCP (as well as prolonged administration of estrogen/progesterone) suppresses FSH. This suppression needs to be countered by artificially causing blood FSH levels to rise in order to cause PAF to AF conversion prior to COS commencing, otherwise pre-antral-to –antral follicle conversion will not take place in an orderly fashion, the duration of ovarian stimulation will be prolonged and both follicle and egg development may be compromised. GnRH agonists (e.g. Lupron, Buserelin, Superfact) , cause an immediate surge in release of FSH by the pituitary gland thus causing conversion from PAF to SAF. This is why, women who take a BCP to launch a cycle of COS need to have an overlap of the BCP with an agonist. By overlapping the BCP with an agonist for a few days prior to menstruation the early recruited follicles are able to complete their developmental drive to the AF stage and as such, be ready to respond appropriately to optimal ovarian stimulation. Using this approach, the timing of the initiation of the IVF treatment cycle can readily and safely be regulated and controlled by varying the length of time that the woman is on the BCP.
Since optimizing follicular response to COS requires that prior to stimulation with gonadotropins, FSH-induced conversion from PAF to AF’s first be completed and the BCP suppresses FSH, it follows when it comes to women launching COS coming off a BCP something needs to be done to cause a rise in FSH for 5-7 days prior to menstruation heralding the cycle of CO S.This is where overlapping the BCP with an agonist (e.g. Lupron/Superfact/Buserelin) comes in. The agonist causes FSH to be released by the pituitary gland and if overlapped with the BCP for several days and this will (within 2-5 days) facilitate PAF to AF conversion…. in time to start COS with the onset of menstruation. Initiating ovarian stimulation in women taking a BCP, without doing this is suboptimal
I believe it to be essential regardless of the protocol of COS protocol being contemplated, for women who launching ovarian stimulation coming off a BCP to overlap with an agonist for several days in advance of initiating ovarian stimulation with the onset of menstruation,
Geoff Sher
____________________________________________________________
ADDITIONAL INFORMATION:
I am attaching online links to two E-books which I recently co-authored with my partner at SFS-NY (Drew Tortoriello MD)……. for your reading pleasure:
1.From In Vitro Fertilization to Family: A Journey with Sher Fertility Solutions (SFS) “
https://sherfertilitysolutions.com/sher-fertility-solutions-ebook.pdf
https://drive.google.com/file/d/1iYKz-EkAjMqwMa1ZcufIloRdxnAfDH8L/view
