Ask Our Doctors – Archive
Our Medical Directors are outstanding physicians that you will find to be very personable and compassionate, who take care to ensure that you have the most cutting-edge fertility treatments at your disposal. This is your outlet to ask your questions to the doctors.
Hi Sher,
Greetings!!
My name is Ajay and my wife is Lakshmi from Albany NY.
Below is our history of treatment in India from 2008 until 2014.
LAKSHMI (Wife)
– UNDERGONE LAPROSCOPIC OVERIAN CYSTECTOMY DONE UNDER GA ON MARCH 11 2009.
– MULTIPLE ENDOMETRIOTIC SPOT IN THE POD, PARIETAL PERITONEUM AND OMENTUM
– LEFT OVARIAN CYST 7X8 cm and RIGHT OVARY AND FALLOPIAN TUBE NORMAL
– TREATED WITH INJ ZOLADEX FOR 3 MONTHS IN VIEW OF ENDOMETERIOSIS
– UNDERGONE 9 IUI’S BETWEEN 2009 TO 2013 WITH NONE SUCCESSFUL.
– HSG (TUBAL CANNULATION) ON DEC 2011. RESULT: BOTH TUBES PATENT WITH FREE SPILLAGE.
– AMH ON AUG 2014 WITH 2.18 ng/ml (LOW FERTILITY).
– HYSTEROSCOPY WITH TB – PCR ON SEP 2014 RESULT: NORMAL AND PATENT.
– NK CELL EVALUATION: %CD 16,56: 8.9 AND ABSOLUTE CD16+56: 167.
– ICSI : FAILED ON SEP 2014 – NONE FERTILIZED EGGS.
AJAY (Husband)
– Semen Analysis: normal count with motility issues.
We have seen and understood many of your videos on Endometriosis and IVF related issues and contacted you from India late 2014 for your advice (after our failed IVF). We need your opinon on how to proceed now with treatment – when and where to see you (as we need to travel from Albany NY)
Thanks
Endometriosis is a condition that occurs when the uterine lining (endometrium) grows not only in the interior of the uterus but in other areas, such as the fallopian tubes, ovaries and the bowel. Endometriosis is a complex condition where, the lack or relative absence of an overt anatomical barrier to fertility often belies the true extent of reproductive problem(s).
All too often the view is expounded that the severity of endometriosis-related infertility is inevitably directly proportionate to the anatomical severity of the disease itself, thereby implying that endometriosis causes infertility primarily by virtue of creating anatomical barriers to fertilization. This over-simplistic and erroneous view is often used to support the performance of many unnecessary surgeries for the removal of small innocuous endometriotic lesions, on the basis of such “treatment” evoking an improvement in subsequent fertility.
It is indisputable that even the mildest form of endometriosis can compromise fertility. It is equally true that, mild to moderate endometriosis is by no means a cause of absolute “sterility”.
Rather, when compared with normally ovulating women of a similar age who do not have endometriosis, women with mild to moderate endometriosis are about four to six times less likely to have a successful pregnancy.
Endometriosis often goes unnoticed for many years. Such patients are frequently, erroneously labeled as having “unexplained infertility”, until the diagnosis is finally clinched through direct visualization of the lesions at the time of laparoscopy or laparoscopy. Not surprisingly, many patients with so called “unexplained” infertility, if followed for a number of years, will ultimately reveal endometriosis.
Women who have endometriosis are much more likely to be infertile. There are several reasons for this:
•First-Ovulation Dysfunction: In about 25 – 30% of cases, endometriosis is associated with ovulation dysfunction. Treatment requires controlled ovarian stimulation (COS). The problem is that the toxic pelvic environment markedly reduces the likelihood that anything other than IVF will enhance pregnancy potential.
•Second- Toxic Pelvic environment that compromises Fertilization Endometriosis is associated with the presence of toxins in peritoneal secretions while it is tempting to assert that normally ovulating women with mild to moderate endometriosis would have no difficulty in conceiving if their anatomical disease is addressed surgically or that endometriosis-related infertility is confined to cases with more severe anatomical disease…nothing could be further from the truth. The natural conception rate for healthy ovulating women in their early 30’s (who are free of endometriosis) is about 15% per month of trying and 70% per year of actively attempting to conceive. Conversely, the conception rate for women of a comparable age who have mild or moderate pelvic endometriosis (absent or limited anatomical disease) is about 5-6% per month and 40% after 3 years of trying. As sperm and egg(s) travel towards the fallopian tubes they are exposed to these toxins which compromise the fertilization process. In fact it has been estimated that there is a 5-6 fold reduction in fertilization potential because of these toxins which cannot be eradicated. Frankly, it really does not matter whether an attempt is made to remove endometriosis deposits surgically as this will not improve pregnancy potential. The reason is that for every deposit observed, there are numerous others that are in the process of developing and are not visible to the naked eye and whether visible or not, such translucent deposits still produce toxins. This also explains why surgery to remove visible endometriosis deposits, controlled ovarian stimulation with or without intrauterine insemination will usually not improve pregnancy potential. Only IVF, through removing eggs before they are exposed to the toxic pelvic environment, fertilizing them in-vitro and then transferring the embryos to the uterus represents the only way to enhance pregnancy potential.
•Third-Pelvic adhesions and Scarring: In its most severe form, endometriosis is associated with scarring and adhesions in the pelvis, resulting in damage to, obstruction or fixation of the fallopian tubes to surrounding structures, thereby preventing the union of sperm and eggs.
•Fourth-Ovarian Endometriomas, Advanced endometriosis is often associated with ovarian cysts (endometriomas/chocolate cysts) that are filled with altered blood and can be large and multiple. When these are sizable (>1cm) they can activate surrounding ovarian connective tissue causing production of excessive male hormones (androgens) such as testosterone and androstenedione. Excessive ovarian androgens can compromise egg development in the affected ovary (ies) resulting in an increased likelihood of numerical chromosomal abnormalities (aneuploidy) and reduced egg/embryo competency”. In my opinion large ovarian endometriomas need to be removed surgically or rough sclerotherapy before embarking on IVF.
•Fifth- Immunologic Implantation Dysfunction (IID). Endometriosis, regardless of its severity is associated with immunologic implantation dysfunction linked to activation of uterine natural killer cells (NKa) and cytotoxic uterine lymphocytes (CTL) in about 30 of cases. This is diagnosed by testing the woman’s blood for NKa using the K-562 target cell test or by endometrial biopsy for cytokine analysis, and, for CTL by doing a blood immunophenotype. These NKa attack the invading trophoblast cells (developing “root system” of the embryo/early conceptus) as soon as it tries to gain attachment to the uterine wall. In most cases, this results in death of the embryo even before the pregnancy is diagnosed and sometimes, in a chemical pregnancy or even an early miscarriage. . As such, many women with endometriosis, rather than being infertile, in the strict sense of the word, often actually experience repeated undetected “mini-miscarriages”.
Advanced Endometriosis: In its most advanced stage, anatomical disfiguration is causally linked to the infertility. In such cases, inspection at laparoscopy or laparoscopy will usually reveal severe pelvic adhesions, scarring and “chocolate cysts”. However, the quality of life of patients with advanced endometriosis is usually so severely compromised by pain and discomfort, that having a baby is often low on the priority list. Accordingly, such patients are usually often more interested in relatively radical medical and surgical treatment options (might preclude a subsequent pregnancy), such as removal of ovaries, fallopian pubis and even the uterus, as a means of alleviating suffering.
Moderately Severe Endometriosis. These patients have a modest amount of scarring/ adhesions and endometriotic deposits which are usually detected on the ovaries, fallopian tubes, bladder surface and low in the pelvis, behind the uterus. In such cases, the fallopian tubes are usually opened and functional.
Mild Endometriosis: These patients who at laparoscopy or laparotomy are found to have no significant distortion of pelvic anatomy are often erroneously labeled as having “unexplained” infertility. To hold that the there can only infertility can only be attributed to endometriosis if significant anatomical disease can be identified, is to ignore the fact that, biochemical, hormonal and immunological factors profoundly impact fertility. Failure to recognize this salient fact continues to play havoc with the hopes and dreams of many infertile endometriosis patients.
TREATMENT:
The following basic concepts apply to management of endometriosis-related infertility:
1.Controlled Ovulation stimulation (COS) with/without intrauterine insemination (IUI): Toxins in the peritoneal secretions of women with endometriosis exert a negative effect on fertilization potential regardless of how sperm reaches the fallopian tubes. This helps explain why COS with or without IUI will usually not improve the chances of pregnancy (over no treatment at all) in women with endometriosis. IVF is the only way by which to bypass this problem.
2.Laparoscopy orLaparotomy Surgery aimed at restoring the anatomical integrity of the fallopian tubes does not counter the negative influence of toxic peritoneal factors that inherently reduce the chances of conception in women with endometriosis four to six fold. Nor does it address the immunologic implantation dysfunction (IID) commonly associated with this condition. Pelvic surgery is relatively contraindicated for the treatment of infertility associated with endometriosis, when the woman is more than 35 years of age. With the pre-menopause approaching, such women do not have the time to waste on such less efficacious alternatives. In contrast, younger women who have time on their side might consider surgery as a viable option. Approximately 30 -40 percent of women under 35 years of age with endometriosis will conceive with in two to three years following corrective pelvic surgery.
3.Sclerotherapy for ovarian endometriomas.: About 10 years ago I introduced “sclerotherapy”, a relatively non-invasive, safe and effective outpatient method to permanently eliminate endometriomas without surgery being required. Sclerotherapy for ovarian endometriomas involves needle aspiration of the liquid content of the endometriotic cyst, followed by the injection of 5% tetracycline into the cyst cavity. Treatment results in disappearance of the lesion within 6-8 weeks, in more than 75% of cases so treated. Ovarian sclerotherapy can be performed under local anesthesia or under general anesthesia. It has the advantage of being an ambulatory office- based procedure, at low cost, with a low incidence of significant post-procedural pain or complications and the avoidance of the need for laparoscopy or laparotomy
4.The role of selective immunotherapy Women with antiphospholipid antibodies (APA’s) experience improved IVF birth rates when heparinoids (Clexane/Lovenox) is administered from the onset of ovarian stimulation with gonadotropins until the 10th week of pregnancy.
a.About Intralipid (IL) and steroid therapy: Intralipid (IL) is a solution of small lipid droplets suspended in water. When administered intravenously, IL provides essential fatty acids, linoleic acid (LA), an omega-6 fatty acid, alpha-linolenic acid (ALA), an omega-3 fatty acid.IL is made up of 20% soybean oil/fatty acids (comprising linoleic acid, oleic acid, palmitic acid, linolenic acid and stearic acid) , 1.2% egg yolk phospholipids (1.2%), glycerin (2.25%) and water (76.5%).IL exerts a modulating effect on certain immune cellular mechanisms largely by down-regulating activated natural killer cells (NKa). This effect is enhanced through the concomitant administration of corticosteroids such as dexamethasone, prednisone, and prednisolone which enhance the therapeutic effect by suppressing cytotoxic/activated T-lymphocytes (CTL). This effect of IL might is likely due to its ability to
5. In vitro fertilization is the treatment of choice for women with endometriosis. This is especially true for women more than 35 years of age or where surgery and treatment with fertility agents has proven to be unsuccessful. We anticipate that approximately 75 percent of such women will achieve the birth of one or more babies within three IVF attempts performed at SIRM.
6.
?suppresses pro-inflammatory cellular (Type-1) cytokines such as interferon gamma and TNF-alpha. In-vitro testing has shown that IL successfully and completely down-regulates activated natural killer cells (NKa) within 2-3 weeks in 78% of women experiencing immunologic implantation dysfunction. In this regard it is just as effective as Intravenous Gamma globulin (IVIg) but at a fraction of the cost and with a far lower incidence of side-effects. Its effect lasts for 4-9 weeks when administered in early pregnancy.
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)
•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
•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)
•Controlled Ovarian Stimulation (COS) in Older women and Women who have Diminished Ovarian Reserve (DOR): A Rational Basis for Selecting a Stimulation Protocol
•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)
•Natural Killer Cell Activation (NKa) and Immunologic Implantation Dysfunction in IVF: The Controversy!
•A personalized, stepwise approach to IVF
•How Many Embryos should be transferred: A Critical Decision in IVF.
•Endometriosis and Infertily
•Treating Ovarian Endometriomas with Sclerotherapy.
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.
Is ICSI an entirely different procedure than IVF or is it done in conjunction with IVF? ( For a patient with 0 or 0.5 morphology)
It is done in conjunction with IVF.
ICSI involves the direct injection of a single sperm into each egg under direct microscopic vision. The successful performance of ICSI requires a high level of technical expertise. In centers of excellence, when ICSI is employed, the IVF birth rate is unaffected by the presence and severity of male infertility. In fact, even when there is an absence of sperm in the ejaculate such as occurs in cases of Congenital Absence of the Vas deferens, when a man is born without these major sperm collecting ducts, in cases where the vasa deferentia are obstructed (such as follwing vasectomy or trauma), and in some cases of testicular failure or where the man has impotency, ICSI can be performed with sperm obtained through Testicular Sperm Extraction (TESE), or aspiration (TESA). In such cases, the birth rate is usually no different than when IVF is performed for indications other than male infertility.
The introduction of ICSI has made it possible to fertilized eggs with sperm derived from men with the severest degrees of male infertility and in the process to achieve pregnancy rates as high, if not higher than that which can be achieved through conventional IVF performed in cases of non–male factor related infertility. The performance of ICSI in cases of “male factor infertility ” has been shown to slightly increase the risk of certain embryo chromosome deletions (leading to a slight increase in early miscarriages) as well as the potential for a resulting male offspring to have male infertility in later life, there is no evidence of any significant increase in the incidence of serious birth defects attributable to the ICSI procedure itself. More relevant is the fact that when ICSI is performed for indications OTHER THAN male infertility there is NO reported increase in the risk of subsequent embryo chromosome deletions, miscarriages or in the incidence of subsequent male factor infertility in the offspring.”
Another major advantage of doing conventional ICSI is that it affords the oportunity to remove the cunmulus complex of cells that envelop the harvested egg and so enable the embryologist to evaluate microscopic paramaters that point to maturity. This cannot be done with conventional IVF as the removal of these cells would virtually preclude conventional fertilization in the petri dish.
A relatively recent study was performed in Sweden, in which 542 children conceived naturally were compared with 941 children conceived through IVF, and IUCS( (440- by conventional IVF & 541 – ICSI) . The following parameters were assessed at birth and during the first 5 years of life:
•Birth health and obstetrical complications
•Birth defects or malformations
•Family relationships
•Physical development
•Mental, psychological, and social development
No major differences in birth weight, growth, total IQ, motor development, and behavior problems or parental stress were found between the children conceived with infertility treatments and those conceived naturally.
About 12-15% of conventional IVF is associated with unanticipated absent or poor fertilization. This has led many to conclude that male infertility may be an “occult phenomenon” in some men. In fact new tests of sperm DNA integrity (SDI) have demonstrated that DNA damage may be present in sperm from men ith both normal and abnormal semen analyses and that male inertility is equally prevalent in such cases.Thus disappointments associated with unanticipated failed fertilization that might be averted through routine performance of ICSI. There simply does not seem to be any practical downside to this aproach which is now routine throughout the SIRM system.
There are no data suggesting that ICSI should not be performed in all cases of in-vitro conception. In all cases, female factor or male factor (normal or abnormal spermatozoa), the use of ICSI bypasses most dysfunctions, eliminating the majority of barriers to fertilization. If fertilization does still not occur, then there is a greater chance of it being a genetic reason, and the risk of genetic abnormalities in normal spermatozoa should not be of greater concern than those in abnormal spermatozoa.
In summary, both the safety and scientific viewpoints strongly support the use of ICSI for all indications.
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)
•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
•Male Factor Infertility
•Hormonal Treatment of Male Infertility
•Antisperm Antibodies, Infertility and the Role of IVF with Intracytoplasmic Sperm Injection?
•Varicocele and Male Infertility: When and how should it be treated.
•The Sperm Chromatin Structure Assay (SCSA): A Measure of the Potential of Sperm to Help Propagate a Viable Pregnancy
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.
What effect does endometriosis have on egg quality? Does even stage 1 endometriosis have harmful effects? What can be done to combat that issue? I have had a lap in which a spot less than 2 cm was removed, but nothing else was found. Thank you.
I do not think it will directly affect egg quality in that scenario.
Endometriosis is a condition that occurs when the uterine lining (endometrium) grows not only in the interior of the uterus but in other areas, such as the fallopian tubes, ovaries and the bowel. Endometriosis is a complex condition where, the lack or relative absence of an overt anatomical barrier to fertility often belies the true extent of reproductive problem(s).
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)
•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
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.
All too often the view is expounded that the severity of endometriosis-related infertility is inevitably directly proportionate to the anatomical severity of the disease itself, thereby implying that endometriosis causes infertility primarily by virtue of creating anatomical barriers to fertilization. This over-simplistic and erroneous view is often used to support the performance of many unnecessary surgeries for the removal of small innocuous endometriotic lesions, on the basis of such “treatment” evoking an improvement in subsequent fertility.
It is indisputable that even the mildest form of endometriosis can compromise fertility. It is equally true that, mild to moderate endometriosis is by no means a cause of absolute “sterility”.
Rather, when compared with normally ovulating women of a similar age who do not have endometriosis, women with mild to moderate endometriosis are about four to six times less likely to have a successful pregnancy.
Endometriosis often goes unnoticed for many years. Such patients are frequently, erroneously labeled as having “unexplained infertility”, until the diagnosis is finally clinched through direct visualization of the lesions at the time of laparoscopy or laparoscopy. Not surprisingly, many patients with so called “unexplained” infertility, if followed for a number of years, will ultimately reveal endometriosis.
Women who have endometriosis are much more likely to be infertile. There are several reasons for this:
•First-Ovulation Dysfunction: In about 25 – 30% of cases, endometriosis is associated with ovulation dysfunction. Treatment requires controlled ovarian stimulation (COS). The problem is that the toxic pelvic environment markedly reduces the likelihood that anything other than IVF will enhance pregnancy potential.
•Second- Toxic Pelvic environment that compromises Fertilization Endometriosis is associated with the presence of toxins in peritoneal secretions while it is tempting to assert that normally ovulating women with mild to moderate endometriosis would have no difficulty in conceiving if their anatomical disease is addressed surgically or that endometriosis-related infertility is confined to cases with more severe anatomical disease…nothing could be further from the truth. The natural conception rate for healthy ovulating women in their early 30’s (who are free of endometriosis) is about 15% per month of trying and 70% per year of actively attempting to conceive. Conversely, the conception rate for women of a comparable age who have mild or moderate pelvic endometriosis (absent or limited anatomical disease) is about 5-6% per month and 40% after 3 years of trying. As sperm and egg(s) travel towards the fallopian tubes they are exposed to these toxins which compromise the fertilization process. In fact it has been estimated that there is a 5-6 fold reduction in fertilization potential because of these toxins which cannot be eradicated. Frankly, it really does not matter whether an attempt is made to remove endometriosis deposits surgically as this will not improve pregnancy potential. The reason is that for every deposit observed, there are numerous others that are in the process of developing and are not visible to the naked eye and whether visible or not, such translucent deposits still produce toxins. This also explains why surgery to remove visible endometriosis deposits, controlled ovarian stimulation with or without intrauterine insemination will usually not improve pregnancy potential. Only IVF, through removing eggs before they are exposed to the toxic pelvic environment, fertilizing them in-vitro and then transferring the embryos to the uterus represents the only way to enhance pregnancy potential.
•Third-Pelvic adhesions and Scarring: In its most severe form, endometriosis is associated with scarring and adhesions in the pelvis, resulting in damage to, obstruction or fixation of the fallopian tubes to surrounding structures, thereby preventing the union of sperm and eggs.
•Fourth-Ovarian Endometriomas, Advanced endometriosis is often associated with ovarian cysts (endometriomas/chocolate cysts) that are filled with altered blood and can be large and multiple. When these are sizable (>1cm) they can activate surrounding ovarian connective tissue causing production of excessive male hormones (androgens) such as testosterone and androstenedione. Excessive ovarian androgens can compromise egg development in the affected ovary (ies) resulting in an increased likelihood of numerical chromosomal abnormalities (aneuploidy) and reduced egg/embryo competency”. In my opinion large ovarian endometriomas need to be removed surgically or rough sclerotherapy before embarking on IVF.
•Fifth- Immunologic Implantation Dysfunction (IID). Endometriosis, regardless of its severity is associated with immunologic implantation dysfunction linked to activation of uterine natural killer cells (NKa) and cytotoxic uterine lymphocytes (CTL) in about 30 of cases. This is diagnosed by testing the woman’s blood for NKa using the K-562 target cell test or by endometrial biopsy for cytokine analysis, and, for CTL by doing a blood immunophenotype. These NKa attack the invading trophoblast cells (developing “root system” of the embryo/early conceptus) as soon as it tries to gain attachment to the uterine wall. In most cases, this results in death of the embryo even before the pregnancy is diagnosed and sometimes, in a chemical pregnancy or even an early miscarriage. . As such, many women with endometriosis, rather than being infertile, in the strict sense of the word, often actually experience repeated undetected “mini-miscarriages”.
Advanced Endometriosis: In its most advanced stage, anatomical disfiguration is causally linked to the infertility. In such cases, inspection at laparoscopy or laparoscopy will usually reveal severe pelvic adhesions, scarring and “chocolate cysts”. However, the quality of life of patients with advanced endometriosis is usually so severely compromised by pain and discomfort, that having a baby is often low on the priority list. Accordingly, such patients are usually often more interested in relatively radical medical and surgical treatment options (might preclude a subsequent pregnancy), such as removal of ovaries, fallopian pubis and even the uterus, as a means of alleviating suffering.
Moderately Severe Endometriosis. These patients have a modest amount of scarring/ adhesions and endometriotic deposits which are usually detected on the ovaries, fallopian tubes, bladder surface and low in the pelvis, behind the uterus. In such cases, the fallopian tubes are usually opened and functional.
Mild Endometriosis: These patients who at laparoscopy or laparotomy are found to have no significant distortion of pelvic anatomy are often erroneously labeled as having “unexplained” infertility. To hold that the there can only infertility can only be attributed to endometriosis if significant anatomical disease can be identified, is to ignore the fact that, biochemical, hormonal and immunological factors profoundly impact fertility. Failure to recognize this salient fact continues to play havoc with the hopes and dreams of many infertile endometriosis patients.
TREATMENT:
The following basic concepts apply to management of endometriosis-related infertility:
1.Controlled Ovulation stimulation (COS) with/without intrauterine insemination (IUI): Toxins in the peritoneal secretions of women with endometriosis exert a negative effect on fertilization potential regardless of how sperm reaches the fallopian tubes. This helps explain why COS with or without IUI will usually not improve the chances of pregnancy (over no treatment at all) in women with endometriosis. IVF is the only way by which to bypass this problem.
2.Laparoscopy orLaparotomy Surgery aimed at restoring the anatomical integrity of the fallopian tubes does not counter the negative influence of toxic peritoneal factors that inherently reduce the chances of conception in women with endometriosis four to six fold. Nor does it address the immunologic implantation dysfunction (IID) commonly associated with this condition. Pelvic surgery is relatively contraindicated for the treatment of infertility associated with endometriosis, when the woman is more than 35 years of age. With the pre-menopause approaching, such women do not have the time to waste on such less efficacious alternatives. In contrast, younger women who have time on their side might consider surgery as a viable option. Approximately 30 -40 percent of women under 35 years of age with endometriosis will conceive with in two to three years following corrective pelvic surgery.
3.Sclerotherapy for ovarian endometriomas.: About 10 years ago I introduced “sclerotherapy”, a relatively non-invasive, safe and effective outpatient method to permanently eliminate endometriomas without surgery being required. Sclerotherapy for ovarian endometriomas involves needle aspiration of the liquid content of the endometriotic cyst, followed by the injection of 5% tetracycline into the cyst cavity. Treatment results in disappearance of the lesion within 6-8 weeks, in more than 75% of cases so treated. Ovarian sclerotherapy can be performed under local anesthesia or under general anesthesia. It has the advantage of being an ambulatory office- based procedure, at low cost, with a low incidence of significant post-procedural pain or complications and the avoidance of the need for laparoscopy or laparotomy
4.The role of selective immunotherapy Women with antiphospholipid antibodies (APA’s) experience improved IVF birth rates when heparinoids (Clexane/Lovenox) is administered from the onset of ovarian stimulation with gonadotropins until the 10th week of pregnancy.
a.About Intralipid (IL) and steroid therapy: Intralipid (IL) is a solution of small lipid droplets suspended in water. When administered intravenously, IL provides essential fatty acids, linoleic acid (LA), an omega-6 fatty acid, alpha-linolenic acid (ALA), an omega-3 fatty acid.IL is made up of 20% soybean oil/fatty acids (comprising linoleic acid, oleic acid, palmitic acid, linolenic acid and stearic acid) , 1.2% egg yolk phospholipids (1.2%), glycerin (2.25%) and water (76.5%).IL exerts a modulating effect on certain immune cellular mechanisms largely by down-regulating activated natural killer cells (NKa). This effect is enhanced through the concomitant administration of corticosteroids such as dexamethasone, prednisone, and prednisolone which enhance the therapeutic effect by suppressing cytotoxic/activated T-lymphocytes (CTL). This effect of IL might is likely due to its ability to
5. In vitro fertilization is the treatment of choice for women with endometriosis. This is especially true for women more than 35 years of age or where surgery and treatment with fertility agents has proven to be unsuccessful. We anticipate that approximately 75 percent of such women will achieve the birth of one or more babies within three IVF attempts performed at SIRM.
6.
?suppresses pro-inflammatory cellular (Type-1) cytokines such as interferon gamma and TNF-alpha. In-vitro testing has shown that IL successfully and completely down-regulates activated natural killer cells (NKa) within 2-3 weeks in 78% of women experiencing immunologic implantation dysfunction. In this regard it is just as effective as Intravenous Gamma globulin (IVIg) but at a fraction of the cost and with a far lower incidence of side-effects. Its effect lasts for 4-9 weeks when administered in early pregnancy.
1.
Dear Dr Sher,
Thank you for taking the time to answer my question. My husband has CBAVD and we have undergone one round of ICSI. From that, we had good quality embryos that resulted in 2 fails and one biochemical pregnancy. I have psoriatic arthritis and at the time was not taking any medication for the first 2 failed transfers and then low dose prednisone for the biochemical. That was two years ago. Unrelated to IVF, I have since commenced treatment with Enbrel. The Enbrel has reduced my disease activity greatly, however my recent bt showed I had a raised platelet count. Going forward into a new round of IVF, I would like to be smarter when it comes to considering the autoimmune issues I have (especially as I suspect that the prednisone did some good). Having a read through some of your material, you state that you would use steroids and intralipids as an approach to autoimmune issues, however I also read that you suspect that the use of tnf blockers may do more harm than good during implantation. My question is (with consideration of our previous response to ivf) what would be your approach with a patient with inflammatory arthritis? Do you think I would benefit from intralipid/steroid/clexane treatment? What is your opinion of arthritis patients using tnf blockers during ivf (assuming the disease activity is low)? Is it helpful or harmful?
I’d like to thank you in advance. Any advice would be gratefully accepted.
Kind regards,
J.A.
Hi J.A.
Thanks for posting here!
First, only if the arthritis is associated with uterine NK cell activation would I recommend Intralipid/steroid therapy. I would NOT use it empirically.
Second, I believe that preimplantation use of TNF alpha blockers can be harmful because in the earliest stage of implantation some TH-1 cytokine activity is needed. Use of such blockers after implantation for threatened miscarriage when there is evidence of NK cell activation might be of be4nefit, but not as a lead in to IVF.
I advise you to ask your doctor to send your blood to one of the Reproductive Immunology Reference labs (I use Reproductive Immunology Associates in Van Nuys, CA) for NK cell activity testing (K-562 target cell blood test), antiphospholipid antibldy (APA) panel and a reproductive immunophenotype (RIP).
Miriam
Miriam.bebawy@hotmail.com
83.76.195.184In reply to Dr. Geoffrey Sher.
Thanks a lot Dr. Sher for your prompt feedback. For the name , i would kindly like to change it to Jil. Thanks a lot again for your thoughts.
Dear Doctor, Thank you so much for your prompt reply. I am indeed grateful. I am extremely worried, I will definitely look in to the points you mentioned and read the articles. I was completely devastated when the Doc told me about my egg situation so I just kept reading about it acquiring more information online. Just didn’t want to give up.My RE took the NCIVF approach as he said I could be a poor responder to stimulated IVF. We started treatment last year,tried IUIs but didn’t work, then 2 NIvf last year . The first time the egg didn’t fertilize and 2nd time it did not implant. We schedule another cycle but my hormones were not okay we had to cancel in November . So we took a break and in Jan 2016 I was pregnant on my own which resulted in D&C. Well, I was told we could go ahead with Stimulated IVF but I wanted to give it a last try this month.I hope and pray that the embryo implants and I able to maintain the pregnancy this time. Will certainly check with my clinic if they have done any IID check and get back to you. Maybe take a Skype appointment with you ASAP.Best regards.
Hi BD,
I wish you well and please stay in touch!
Geoff Sher