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.
Respected sir,
I am 23 years old, I am facing the problem is sperm agglutination, please told me treatment or preventing measures. Thanks
It is likely that your husband harbors sperm antibodies. If I am correct then you will 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.
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.
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.
•Controlled Ovarian Stimulation (COS) for IVF: Selecting the ideal protocol
•IVF: Factors Affecting Egg/Embryo “competency” during Controlled Ovarian Stimulation(COS)
•Antisperm Antibodies, Infertility and the Role of IVF with Intracytoplasmic Sperm Injection (ICSI)
Please call or email Julie Dahan, my patient concierge. She will guide you on how to set up an in-person or Skype consultation with me. You can reach Julie at on her cell phone or via email at any time:
Julie Dahan
•Email: Julied@sherivf.com
•Phone: 702-533-2691
?800-780-7437
Geoff Sher
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.
Dear Dr Sher
Following a miscarriage @ 10w of a chromosomally normal conceptus, I underwent a battery of tests
NK cytoxicity assay showed elevated NK cells, therefore in my recent FET, we treated with both prednisolone and intralipids. We transferred a single euploid (PGS tested with NGS) blastocyst, however this resulted in a chemical pregnancy
In Jan I achieved successful implantation after ET of a euploid blast *without* treatment for IID (with suboptimal uterine lining of 7mm at hCG trigger)
However I did NOT propagate a pregnancy in my recent FET of a euploid blast *with* steroids/IL (with uterine lining at 9mm upon initiation of progesterone)
One of the leading clinics in reproductive immunology in the UK advocates for endometrial biopsy to test for elevated uterine NK cells (CD57+) and diminished Fox P3 (regulatory) cells.
Prof Quenby and Brosens argue that even if peripheral blood NK cells levels are elevated, if uNK cells are too *low*, that treating with steroids/IL can do more harm than good – because some inflammation is necessary to support implantation
I have not yet had the endometrial biopsy test (done serially in different cycles for more than one single month’s level) to ascertain my uNK levels
In your opinion, could the pred/IL have done more harm than good?
What other explanation could you offer for failed implantation WITH treatment for IID and a good uterine lining, vs successful implantation WITHOUT treatment for IID and a suboptimal uterine lining?
With very many thanks and warmest regards
Katy
I very respectfully do not agree with this proposition at all. I would also point out that the gold standard test for activated natural killer cells is then K-562 target cell test. To the best of my knowledge there is no Reproductive Immunology Reference Laboratory in the UJK that performs this test with adequate reliability. There are only about 4 or 5 such laboratories in the U.S.A that can do the K-562 test properly. I use Reproductive Immunology Associates (RFIA) in Van Nuys, CA and have my UK patients send there blood FEDEX overnight to them. I suggest that your blood be sent there (you can find them ob Google). The uterine cytokine test can also be used, but in my opinion it is not nearly as reliable. Also have RIA match your and your husband’s blood for DQA alpha/HLA genotypic similarities because if that exists, treatment would need to be modified significantly. Finally please know that the NKa test differs from the concentration of NK cells in your blood. The latter is not relevant.
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.
•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
•Traveling for IVF from Out of State/Country–
Please call or email Julie Dahan, my patient concierge. She will guide you on how to set up an in-person or Skype consultation with me. You can reach Julie at on her cell phone or via email at any time:
Julie Dahan
•Email: Julied@sherivf.com
•Phone: 702-533-2691
?800-780-7437
Geoff Sher
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.
Hi Dr Sher,
I have a very interesting history of pregnancy. I would like to update my history and please provide me your opinion on my case. I am a 27 years old female. I got married at 22. I had a natural pregnancy that resulted in blighted ovum after few months of marriage. I have mild PCOS. I was never pregnant on my own after that. We seeked the help of RE to use Femara for ovulation induction, I conceived naturally after induction on our first try. Things went on well until 20 weeks. In anomaly scan, they found out Grebes syndrome. We thought it was sporadic and went for D and C but I delivered normally before that at 21 weeks. Our fetus was sent for genetic testing and our blood samples were analyzed and we found out that it was not sporadic but genetic. Both me and my husband are carriers of this single gene. We are not related. It is still a mystery to carry that rare genetic disorder. We are completely normal though as carriers. So we opted for IVF with GGD. We went for 2 egg retrievals with 4 chromosomally normal embryos and absence of disorder genes, 10 carries but chromosomally normal and few affected. We had our first FET , few weeks back, thinking that we will be pregnant right away. But it resulted in BFN. No reasons known. Unexplained. Everything looked good. We are so devastated due to these series of disaster. We are getting ready for 2nd FET. They say its just matter of luck but I’m afraid we are overlooking something. I only have 3 embryos to use. I do not want to take another chance and waste them. Please advice what could be done. We live in CA. Thank you. I solely rely on your advice to help me out. Thanks a ton in advance
It is probably bad luck. Remember, the main reason for IVF failure is abnormal numerical chromosomal make-up of the egg that inevitably results in a numerical chromosomal abnormality of the embryo (embryo aneuploidy). This affects 1: 2 eggs in young women and occurs independent of genetic configuration (such as in your case). The tests done for your genetic problem are different to what would be needed to detect embryo aneuploidy. I am not suggesting thatb you should do PGS for aneuploidy. However, I am suggesting that embryo aneuploidy could likely explain the failed IVF, in spite of the embryos not carrying the genetic anomaly.
Good luck with your next FET.
Geoff Sher
Hello Doctor Shed,
I write you because today I had my egg retrieval. Out of 8 follicles they only got 3 eggs. On my first Ivf they got 1 out of 3 follicles.
This second cycle was with Elonva 150 and on day 5 the doctor added 3 ampules of Menogon for four more days. As trigger he used Ovitrelle 250 (both cycles).
During the cycle I had zero blood test done and two ultrasounds (day 5 and day 9).
After the egg retrieval the doctor told us that he just doesn’t have an explanation. He doesn’t say that maybe the protocols he has chosen aren’t adequate. He just said that is something he can’t explain but has nothing to do with the protocol and the trigger shot. He also said that maybe Ivf is not for us.
We have one more Ivf covered by the insurance but decided no to go ahead because we don’t feel we’re getting the answers we need from him.
We are considering adoption but would like to have another honest opinion.
I’m 29 years old. AMH 1.92, high male hormones and minimal endometriosis with no symptoms other that infertility. We’ve been trying to conceive for 1 year and a half. I had a laparoscopy to remove endometriosis 3 months ago.
Husband sperm is fine.
I really appreciate your opinion on this subject.
Thanks in advance
I’d also like to add that we’ve had 3 Clomid + trigger shots cycles with timed intercourse before the laparoscopy to remove endometriosis. And two Ivf cycles.
We haven’t tried anything else.
Without knowing much more about you, I cannot advise authoritatively. I can tell you that this could have to do with the protocol used for stimulation and/or the Ovidrel dosage used for the trigger. Please read the articles referenced bedlow carefully.
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.
•Implications of “Empty Follicle Syndrome and “Premature Luteinization”
•Premature Luteinization (“the premature LH surge): Why it happens and how it can be prevented.
•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 Aproach
•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?
•Traveling for IVF from Out of State/Country–
•A personalized, stepwise approach to IVF
Please call or email Julie Dahan, my patient concierge. She will guide you on how to set up an in-person or Skype consultation with me. You can reach Julie at on her cell phone or via email at any time:
Julie Dahan
•Email: Julied@sherivf.com
•Phone: 702-533-2691
?800-780-7437
Geoff Sher
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.
Hello Dr. Sher,
I’m very curious about the effects of trigger choice on ultimate egg quality. Thank you for your post on your other site, which gave quite a bit of insight to how the trigger and which type/dosage can affect egg maturity.
If you don’t mind, I would love your advice. I just completed round 4 of IVF (with PGS/banking), and depending on how this goes, might need to try again. I have DOR (lowest AMH of 0.25, highest day 3 FSH of 29), so knowing that I won’t be able to make as many follicles / eggs as other women, the quality side becomes extra critical. My 4 rounds have resulted in the following outcomes:
– round 1 (single Ovidrel trigger): 7 follicles, 7 eggs, 6 mature, 5 fertilized, 1 blast frozen (not PGS tested)
– round 2 (double Ovidrel trigger): 2 follicles, 2 eggs, 1 mature, 0 blasts
– round 3 (double Ovidrel trigger): 4 follicles, 2 eggs, 2 mature, 1 blast (PGS – Turners Syndrome)
– round 4 (double Ovidrel + Lupron triggers 12h apart): 5 follicles, 4 eggs, 4 mature, waiting on results now…
My RE explained that the Ovidrel + Lupron trigger was to try to hit the maturity of the eggs from both angles…have you heard of this and/or do you agree? My biggest frustration is that we are able to produce follicles and mature eggs, but can’t seem to get many blasts to succeed to freeze / bank / PGS test. It feels like this final step might be impacting our final blast numbers…i.e we are producing mature eggs, but maybe not euploid mature eggs?
I would love and appreciate your thoughts on this!
Many thanks,
Kelly (Houston, TX)
Probably should have also mentioned, I’m 33 yrs old. 🙂
Hi kelly,
I agree with the decision to double the Ovidrel dosage for trigger and although I do not use combined hCG + Lupron trigger, I accept the rationale for using this (anything is better than a reduced dosage of hCG alone). However, very respectfully, much mofre important is the manner in which women with DOR are stimulated, in my opinion.
Women who (regardless of age) have DOR have a reduced potential for IVF success. Much of this is due to the fact that such women tend to have increased production of LH biological activity which can result in excessive LH-induced ovarian male hormone (predominantly testosterone) production which in turn can have a deleterious effect on egg/embryo “competency”.
While it is presently not possible by any means, to reverse the age-related effect on the woman’s “biological clock, certain ovarian stimulation regimes, by promoting excessive LH production (e.g. short agonist/Lupron- “flare” protocols, clomiphene and Letrozole), can make matters worse. Similarly, the amount/dosage of certain fertility drugs that contain LH/hCG (e.g. Menopur) can have a negative effect on the development of the eggs of older women and those who have DOR and should be limited.
I try to avoid using such protocols/regimes (especially) in women with DOR, favoring instead the use of the agonist/antagonist conversion protocol (A/ACP), a modified, long pituitary down-regulation regime, augmented by adding supplementary human growth hormone (HGH). I further recommend that such women be offered access to embryo banking of PGS (next generation gene sequencing/NGS)-selected normal blastocysts, the subsequent selective transfer of which by allowing them to to capitalize on whatever residual ovarian reserve and egg quality might still exist and thereby “make hay while the sun still shines” could significantly enhance the opportunity to achieve a viable pregnancy
Please visit my new Blog on this very site, 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
•IVF: Factors Affecting Egg/Embryo “competency” during Controlled Ovarian Stimulation(COS)
•The Fundamental Requirements For Achieving Optimal IVF Success
•Ovarian Stimulation for IVF using GnRH Antagonists: Comparing the Agonist/Antagonist Conversion Protocol.(A/ACP) With the “Conventional” Antagonist Approach
•Anti Mullerian Hormone (AMH) Measurement to Assess Ovarian Reserve and Design the Optimal Protocol for Controlled Ovarian Stimulation (COS) in IVF.
•The “Biological Clock” and how it should Influence the Selection and Design of Ovarian Stimulation Protocols for IVF.
• A Rational Basis for selecting Controlled Ovarian Stimulation (COS) protocols in women with Diminished Ovarian Reserve (DOR)
•Diagnosing and Treating Infertility due to Diminished Ovarian Reserve (DOR)
•Controlled Ovarian Stimulation (COS) in Older women and Women who have Diminished Ovarian Reserve (DOR): A Rational Basis for Selecting a Stimulation Protocol
•Human Growth Hormone Administration in IVF: Does it Enhances Egg/Embryo Quality and Outcome?
•The BCP: Does Launching a Cycle of Controlled Ovarian Stimulation (COS). Coming off the BCP Compromise Response?
•Blastocyst Embryo Transfers Should be the Standard of Care in IVF
•Frozen Embryo Transfer (FET) versus “Fresh” ET: How to Make the Decision
•Frozen Embryo Transfer (FET): A Rational Approach to Hormonal Preparation and How new Methodology is Impacting IVF.
•Staggered IVF: An Excellent Option When. Advancing Age and Diminished Ovarian Reserve (DOR) Reduces IVF Success Rate
•Embryo Banking/Stockpiling: Slows the “Biological Clock” and offers a Selective Alternative to IVF-Egg Donation.
•Preimplantation Genetic Testing (PGS) in IVF: It Should be Used Selectively and NOT be Routine.
•Preimplantation Genetic Sampling (PGS) Using: Next Generation Gene Sequencing (NGS): Method of Choice.
•PGS in IVF: Are Some Chromosomally Abnormal Embryos Capable of Resulting in Normal Babies and Being Wrongly Discarded?
•PGS and Assessment of Egg/Embryo “competency”: How Method, Timing and Methodology Could Affect Reliability
•Treating Out-of-State and Out-of-Country Patients at Sher-IVF in Las Vegas:
•Traveling for IVF from Out of State/Country–
•A personalized, stepwise approach to IVF
•How Many Embryos should be transferred: A Critical Decision in IVF.
•The Role of Nutritional Supplements in Preparing for IVF
•Premature Luteinization (“the premature LH surge): Why it happens and how it can be prevented.
•IVF Egg Donation: A Comprehensive Overview
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
800-780-7437
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.