IVF Failure and Implantation Dysfunction: The Role of Endometrial Thickness, Uterine Pasthology and Immunologic Factors

The considerable emotional, physical and financial burden associated with infertility treatment in general and with IVF in specific, demand that factors known to affect outcome be identified and regulated prior to initiating treatment.

Just as a successful garden needs a ”good” seed properly planted in fertile soil to produce healthy plants, successful embryo implantation requires a good seed (genetically “normal” embryo) and fertile soil (receptive uterine lining) to make a healthy baby. I have long used this “Seed/Soil Relationship” analogy to help clarify the critical nature of the interaction between embryo and endometrium in the successful propagation of pregnancy.

There have in the last decade been numerous reports suggesting that certain drugs/supplements (e.g. GCSF) and endometrial receptivity testing/preparation might dramatically improve implantation. As yet, none of these have been proven to be effective. This article addresses the influence of the most relevant and important factors that are known to affect endometrial receptivity and discusses approaches to treatment:

  1. Endometrial thickness

In 1989, I first demonstrated that in both normal and “hormonally stimulated” cycles, preovulatory endometrial thickness as assessed by ultrasound examination, is partially predictive of embryo implantation (pregnancy) potential following IVF. Ideally the endometrium should measure at least 8.0mm in thickness, (but preferably >9mm).

A “poor” endometrial lining is most commonly due to: 1) inflammation of the uterine lining (endometritis) that usually occurs as a result of endometritis (inflammation of the uterine lining that can follow a septic delivery, partial retention of the placenta following delivery, abortion or miscarriage, 2) severe adenomyosis (gross invasion of the uterine muscle by endometrial glandular tissue), 3) multiple fibroid tumors of the uterine wall) 4) prenatal exposure to the synthetic hormone, diethylstilbestrol (DES) and, 5) following >3, consecutive, back to back cycles of clomiphene citrate ovulation induction.

Treatment with vaginal Sildenafil (Viagra): Hitherto, attempts to augment endometrial growth in women with poor endometrial linings by bolstering circulating estrogen blood levels (through the administration of increased doses of fertility drugs, aspirin administration and with supplementary estrogen therapy) have yielded disappointing results.

In the mid-90’s I first reported on the finding that thee vaginal administration of Viagra for several days prior to the “hCG trigger “ or progesterone administration enhances uterine blood flow and estrogen delivery to the uterine lining and so improves endometrial thickening. Then In October 2002, I reported on the administration of vaginal Viagra to 105 women with repeated IVF failure due to persistently thin endometrial linings. All of the women had experienced at least two (2) prior IVF failures attributed to intractably thin uterine linings. About 70% of these women responded to treatment with Viagra suppositories with a marked improvement in endometrial thickness and 45% of these women achieved live IVF- births following a single cycle of treatment with Viagra. Nine percent (9%) miscarried. None of the women who had failed to achieve an improvement in endometrial thickness following Viagra therapy, subsequently and who underwent embryo transfers achieved viable pregnancies.

2.Uterine Pathology:

It has long been suspected that anatomical defects of the uterus might result in infertility.

While myomas (fibroids) embedded deep in the uterine wall, are unlikely to cause infertility, an association between their presence and infertility has been observed in cases where they distort the uterine cavity, or protrude as submucous polyps through the endometrial lining. It would appear that even small sub mucous myomas have the potential to prejudice implantation.

Far too many infertile women found to have a partial or complete septum in the uterus are subjected to surgical excision of the septum with a promise that this will enhance subsequent implantation. This is an erroneous belief. Contrary to popular belief, the presence of a septum that partially or completely partitions the uterine cavity, while being responsible (in some cases) for late miscarriages and premature onset of labor, does NOT cause failed implantation.

It is likely that most surface lesions in the uterine cavity, whether due to an endometrial, placental or fibroid polyp (no matter how small), or intrauterine adhesion’s, have the potential to interfere with implantation by producing a local “inflammatory”- type response, not too dissimilar in nature from that which is caused by a foreign body such as a intrauterine contraceptive device. Unfortunately, a dye X-Ray test (hysterosalpingogram/HSG) will often miss many smaller such lesions. The only reliable methods for diagnosing even the smallest of such lesions, is through the performance of a hysterosongram (HSN),a hysteroscopy or an MRI.  

Hysterosonogram (syn. Saline ultrasound): This procedure involves the trans-cervical injection of a physiological saline solution via a catheter, into the uterine cavity. The fluid distended cavity is then examined by vaginal ultrasound for any irregularities that might point to surface lesions such as polyps, fibroid tumors, scarring, or a uterine septum. If performed correctly, the HSN is highly effective in recognizing even the smallest surface lesions that protrude into the uterine cavity. It is less expensive, less traumatic, and diagnostically, equally reliable as hysteroscopy. The only disadvantage lies in the fact that if a lesion is detected, it may require the subsequent performance of hysteroscopic surgical approach to treating the problem..

Hysteroscopy: Diagnostic hysteroscopy is an office procedure that is performed under intravenous sedation, general or local anesthesia, with minimal discomfort to the patient. The procedure involves the insertion of a thin, lighted, telescopelike instrument known as a hysteroscope through the vagina and cervix into the uterus in order to fully examine the uterine cavity. The uterus is first distended with carbon dioxide gas, which is passed through a sleeve adjacent to the hysteroscope. As is the case with FUS, diagnostic hysteroscopy facilitates examination of the inside of the uterus under direct vision for defects that might interfere with implantation. 

We have observed that approximately 8% of candidates for IVF have intrauterine lesions that require attention prior to undergoing IVF in order to optimize the chances of a successful outcome. We strongly recommend that all patients who have such lesions undergo surgery (D&C and/or hysteroscopic resection) to correct the pathology prior to undergoing IVF. Depending on the severity and nature of the pathology, therapeutic hysteroscopy may require general anesthesia. If so, it should be performed in an outpatient surgical facility or in a conventional operating room.

  1. Immunologic factors

The implantation process begins six or seven days after fertilization of the egg. At this time, specialized embryonic cells (i.e., the trophoblast), which later becomes the placenta; begin growing into the uterine lining. When the trophoblast and the uterine lining meet, they, along with Immune cells in the lining, become involved in a “cross talk” through mutual exchange of hormone-like substances called cytokines. Because of this complex immunologic interplay, the uterus is able to foster the embryo’s successful growth. Thus, from the very earliest stage of implantation the trophoblast establishes a foundation for the future nutritional, hormonal and respiratory interchange between mother and baby. In this manner, the interactive process of implantation is not only central to survival in early pregnancy but also to the quality of life after birth.

Considering its importance, it is not surprising that failure of proper function of this immunologic interaction during implantation has been implicated as a cause of recurrent miscarriage, late pregnancy fetal loss, IVF failure, and infertility. A partial list of immunologic factors that may be involved in these situations includes anti-phospholipid antibodies (APA), antithyroid antibodies (ATA), and most importantly activation of uterine natural killer cells (NKa). Presently, these immunologic markers in the blood can be only adequately measured by a handful of highly specialized reproductive immunology laboratories in the United States. I personally use Reproductive Immunology Associates in Van Nuys, CA or Reprosource in Boston, MA.

The Central role of Natural Killer cells: After ovulation and during early pregnancy, NK cells comprise more than 70% of the immune cell population of the uterine lining. NK cells produce a variety of local hormones known cytokines. Uncontrolled, excessive release of certain cytokines (i.e. TH-1 cytokines) is highly toxic to the trophoblast (“root system”) of the embryo” leading to their programmed death (apoptosis) and, subsequently to failed or compromised/dysfunctional implantation. In the following situations NK cells become activated, and start to produce an excess of TH-1 cytokines:

  • Autoimmune Implantation Dysfunction: This is most commonly seen in association with a personal or family history of autoimmune diseases such as ith conditions such as Rheumatoid arthritis, hypothyroidism endometriosis and Lupus Erythematosus, Scleroderma, Dermatomyositis  etc. It is also encountered in one third of women who have endometriosis (regardless of its severity), and in cases of “unexplained infertility” as well as  with  recurrent pregnancy loss (RPL).
  • Alloimmune implantation dysfunction where the male and female partners share specific genetic (DQ-alpha and/or HLA) similarities  This is commonly seen in cases of RPL and in cases of  secondary infertility

Activated NK cells (NKa) can be detected through the K-562 target cell blood test and (more recently) through uterine biopsy for TH-1 cytokine activity. Treatment involves selective use of Intralipid (IL) or immunoglobulin (IVIG) therapy combined with oral steroids, initiated more 10-14 days prior to embryo transfer and in most cases of alloimmune implantation dysfunction, the transfer of a single blastocyst at a time.

31 Comments

Suzel

Hi dr! I have a thin endometrium. The thickest it ever got was 7.2 with 12mg estrogen daily. I am preparing currently for a donor egg cycle and it is only 5mm. I had 2 D& C previously. But not sure what my endometrium was before the d&cs. Is it possible that a d&c can damage an endometrium to such an extent. I had a hystoroscopy and biopsy and all normal, no infection and no abnormal growths. Viagra will be an opion but is there anything else which could help to improve the thickness? What are the success rates for blood serum injected into the uterus? Any other advice will be greatly appreciated!!

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Dr. Geoffrey Sher

It is very unlikely that a D&C would have damaged your endometrium.

It was as far back as 1989, when I first published a study that examined the correlation between the thickness of a woman’s uterine lining (the endometrium), and the subsequent successful implantation of embryos in IVF patients. This study revealed that when the uterine lining measured <8mm in thickness by the day of the “hCG trigger” (in fresh IVF cycles), or at the time of initiating progesterone therapy (in embryo recipient cycles, e.g. frozen embryo transfers-FET, egg donation-IVF etc.) , pregnancy and birth rates were substantially improved. Currently, it is my opinion, that an ideal estrogen-promoted endometrial lining should ideally measure at least 9mm in thickness and that an endometrial lining measuring 8-9mm is “intermediate”. An estrogenic lining of <8mm is in most cases unlikely to yield a viable pregnancy.

A “poor” uterine lining is usually the result of the innermost layer of endometrium (the basal or germinal endometrium from which endometrium grows) ) not being able to respond to estrogen by propagating an outer, “functional” layer thick enough to support optimal embryo implantation and development of a healthy placenta (placentation). The “functional” layer ultimately comprises 2/3 of the full endometrial thickness and is the layer that sheds with menstruation in the event that no pregnancy occurs.

The main causes of a “poor” uterine lining are:

1. Damage to the basal endometrium as a result of:
a. Inflammation of the endometrium (endometritis) most commonly resulting from infected products left over following abortion, miscarriage or birth
b. Surgical trauma due to traumatic uterine scraping, (i.e. due to an over-aggressive D & C)
2. Insensitivity of the basal endometrium to estrogen due to:
a. Prolonged , over-use/misuse of clomiphene citrate
b. Prenatal exposure to diethylstilbestrol (DES). This is a drug that was given to pregnant women in the 1960’s to help prevent miscarriage
3. Over-exposure of the uterine lining to ovarian male hormones (mainly testosterone): Older women, women with diminished ovarian reserve (poor responders) and women with polycystic ovarian syndrome -PCOS tend to have raised LH biological activity.. This causes the connective tissue in the ovary (stroma/theca) to overproduce testosterone. The effect can be further exaggerated when certain methods for ovarian stimulation such as agonist (Lupron/Buserelin) “flare” protocols and high dosages of menotropins such as Menopur are used in such cases.
4. Reduced blood flow to the basal endometrium:
Examples include;
a. Multiple uterine fibroids - especially when these are present under the endometrium (submucosal)
b. Uterine adenomyosis (excessive, abnormal invasion of the uterine muscle by endometrial glands).

“The Viagra Connection”

Eighteen years ago years ago, after reporting on the benefit of vaginal Sildenafil (Viagra) for to women who had implantation dysfunction due to thin endometrial linings I was proud to announce the birth of the world’s first “Viagra baby.” Since the introduction of this form of treatment, thousands of women with thin uterine linings have been reported treated and many have gone on to have babies after repeated prior IVF failure.

For those of you who aren’t familiar with the use of Viagra in IVF, allow me to provide some context. It was in the 90’s that Sildenafil (brand named Viagra) started gaining popularity as a treatment for erectile dysfunction. The mechanism by which it acted was through increasing penile blood flow through increasing nitric oxide activity. This prompted me to investigate whether Viagra administered vaginally, might similarly improve uterine blood flow and in the process cause more estrogen to be delivered to the basal endometrium and thereby increase endometrial thickening. We found that when Viagra was administered vaginally it did just that! However oral administration was without any significant benefit in this regard. We enlisted the services of a compound pharmacy to produce vaginal Viagra suppositories. Initially, four (4) women with chronic histories of poor endometrial development and failure to conceive following several advanced fertility treatments were evaluated for a period of 4-6 weeks and then underwent IVF with concomitant Viagra therapy. Viagra suppositories were administered four times daily for 8-11 days and were discontinued 5-7 days prior to embryo transfer in all cases.

Our findings clearly demonstrated that vaginal Viagra produced a rapid and profound improvement in uterine blood flow and that was followed by enhanced endometrial development in all four cases. Three (3) of the four women subsequently conceived. I expanded the trial in 2002 and became the first to report on the administration of vaginal Viagra to 105 women with repeated IVF failure due to persistently thin endometrial linings. All of the women had experienced at least two (2) prior IVF failures attributed to intractably thin uterine linings. About 70% of these women responded to treatment with Viagra suppositories with a marked improvement in endometrial thickness. Forty five percent (45%) achieved live births following a single cycle of IVF treatment with Viagra The miscarriage rate was 9%. None of the women who had failed to show an improvement in endometrial thickness following Viagra treatment achieved viable pregnancies.

Following vaginal administration, Viagra is rapidly absorbed and quickly reaches the uterine blood system in high concentrations. Thereupon it dilutes out as it is absorbed into the systemic circulation. This probably explains why treatment is virtually devoid of systemic side effects

It is important to recognize that Viagra will NOT be effective in improving endometrial thickness in all cases. In fact, about 30%-40% of women treated fail to show any improvement. This is because in certain cases of thin uterine linings, the basal endometrium will have been permanently damaged and left unresponsive to estrogen. This happens in cases of severe endometrial damage due mainly to post-pregnancy endometritis (inflammation), chronic granulomatous inflammation due to uterine tuberculosis (hardly ever seen in the United States) and following extensive surgical injury to the basal endometrium (as sometimes occurs following over-zealous D&C’s).

Combining vaginal Viagra Therapy with oral Terbutaline;
In my practice I sometimes recommend combining Viagra administration with 5mg of oral terbutaline. The Viagra relaxes the muscle walls of uterine spiral arteries that feed the basal (germinal) layer of the endometrium while Terbutaline, relaxes the uterine muscle through which these spiral arteries pass. The combination of these two medications interacts synergistically to maximally enhance blood flow through the uterus, thereby improving estrogen delivery to the endometrial lining. The only drawback in using Terbutaline is that some women experience agitation, tremors and palpitations. In such cases the terbutaline should be discontinued. Terbutaline should also not be used women who have cardiac disease or in those who have an irregular heartbeat.
About 75% of women with thin uterine linings see a positive response to treatment within 2-3 days. The ones that do not respond well to this treatment are those who have severely damaged inner (basal/germinal) endometrial linings, such that no improvement in uterine blood flow can coax an improved response. Such cases are most commonly the result of prior pregnancy-related endometrial inflammation (endometritis) that sometimes occurs post abortally or following infected vaginal and/or cesarean delivery.
Viagra therapy has proven to be a god send to thousands of woman who because of a thin uterine lining would otherwise never have been able to successfully complete the journey “from infertility to family”.

To be effective, Viagra must be administered vaginally. It is NOT effective when taken orally. We prescribe 20mg vaginal suppositories to be inserted four times per day. Treatment is commenced soon after menstruation ceases and is continued until the day of the “hCG trigger.” While ideally the treatment should be sustained throughout the first half of the cycle, most women will respond within 48-72 hours. For this reason, Viagra can be used to “rescue” a poor lining after the cycle has already started, provided that there is enough time remaining prior to ovulation, egg retrieval or progesterone administration.

Geoff Sher.

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berashy

does treating a chronic endometritis increase the ivf success? i checked some studies that suggest that there is no difference in the outcome after treatment

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kirti

hi sir.
history trying since 12 months
had been thru septum removal .
and 6cycles of iui failed. not sure wat went wrong. properly timed. ovulation on time. amh 5plus. I feel some problem in implantation. I feel some pain on implantation duration. but next day all gone. often seen small white ball discharged a day later looks like embryo. I m now planning for ivf. pls suggest how can I make sure that if issues are with implantation then what tests I can do or treatments so that my ivf dont fail.

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Dr. Geoffrey Sher

Not sure I would have had the septum surgery. This problem rarely if ever causes infertility in my opinion.

For about 10% of all infertile couples, the cause of the infertility cannot be readily determined using conventional diagnostic methods. Such cases are often referred to as “unexplained infertility.” The truth however is that in most such cases, the diagnosis of “unexplained infertility is in fact “presumptive because a more in-depth evaluation would have revealed a cause. This having been said, people diagnosed with so called “unexplained infertility” fall into two broad groups: a)those couples who don’t have any biological problems interfering with pregnancy and, b) those who do but the reason cannot be found due to insufficient medical information or technology. It is in this latter group that improved testing techniques have made infertility easier to diagnose and treat.
In order to make even a presumptive diagnosis of “unexplained infertility” the answers to the following questions must be in the affirmative.
 Is the woman ovulating normally?
 Is the couple having intercourse regularly in the periovulatory phase of the cycle?
 Are the fallopian tubes normal and open?
 Can endometriosis be excluded?
 Does the male partner have normal semen parameters (most specifically with regard to sperm count and motility?
 Is the post coital (Huhner) test (periovulatory examination of cervical mucous, done 6-18 hours after intercourse) normal?
The definitive diagnosis of “unexplained infertility” has a lot to do with the thoroughness of the health care provider in excluding all possible causes. The fewer tests performed, the more likely a presumptive diagnosis
For Example:
 Abnormalities of the fallopian tubes (adhesions or developmental defects) of the finger-like “petals” at their outer ends of the tubes that help sweep eggs inside (i.e. fimbriae). can prevent eggs from being collected and transported to the awaiting sperm
 Chromosomal abnormalities of eggs or embryos: Eggs must be euploid (contain the right number of chromosomes) to be successfully fertilized and embryos must also be euploid in order to implant successfully in the uterine lining. Until recently there was no reliable method for determining whether eggs and embryos were euploid. The recent introduction of genetic tests such as comparative genomic hybridization (CGH) now allows for identification of all chromosomes in the egg and embryo. As such CGH represents an important addition to the “infertility” diagnostic armamentarium.
 Luteinized Unruptured Follicle (LUF)Syndrome: Here, the eggs can become trapped in the follicle and not be released (trapped ovulation) In such cases routine tests done to detect ovulation ((temperature charting, Urine LH testing, Blood progesterone levels) may be normal resulting in false interpretation that ovulation is actually occurring.
 Ovulation (hormonal) Dysfunction: Abnormalities in ovarian hormone production in the preovulatory phase of the cycle (follicular phase defect) and/or in the postovulatory phase (luteal phase defect) can negatively affect preparation of the uterine lining (endometrium), thus thwarting normal implantation.
 Immunologic implantation dysfunction (IID): Sometimes, the woman’s or the man’s own immune system can attack sperm cells, killing them or causing them to become immobilized. Also, immunologic dysfunction involving the uterine lining can cause the implanting embryo to be rejected so early that the woman does not even recognize that she in fact had conceived.
 Cervical infection; Ureaplasma urealyticum infection of the cervical glands can prevent sperm from migrating through the cervix and uterus to reach the egg(s) in the fallopian tube(s). Such infection will usually not be detectable through routine examination and/or cervical culturing methods.
 Mild or Moderate Endometriosis: Endometriosis is in 100% of cases associated with the production of “pelvic toxins” that reduce the fertilization potential of otherwise normal eggs by a factor of 3-5. In addition, about 1/3 of woman with endometriosis (regardless of its severity) have immunologic implantation dysfunction (IID). Furthermore mild and often even moderately severe endometriosis can only be accurately diagnosed by direct visualization of the lesions through laparoscopy or laparotomy and, the detection of IID requires highly sophisticated tests that can only be adequately performed by a handful of Reproductive Immunology Reference Laboratories in the United States. Finally, a condition called nonpigmented endometriosis, in which the endometrium may be growing inside the pelvic cavity with many of the same deleterious effects as overt endometriosis, cannot be detected even by direct vision (at laparoscopy/laparotomy). The fertility of these patients may be every bit as compromised as if they had detectable endometriosis.
 Psychological Factors: The entire reproductive process is governed by the brain. Thus it should come as no surprise that stress and negativity can interfere with hormonal balance and decrease the ability to conceive.
 Mild Male Factor
 Antisperm antibodies in the man or woman.
Management:
Successful management of “Unexplained Infertility” requires that a very individualized approach be taken. Wherever possible the underlying cause should first be identified. Problems that involve ovulation dysfunction (hormonal imbalance) require ovulation induction with oral or injectible fertility drugs. Cervical mucous hostility due to infection with ureaplasma (which is transferred back and forth sexually to both partners) requires specific and concurrent antibiotic therapy. In other cases involving younger women (under 39 years) where there is a problem with sperm migration via the cervix and uterus to the fallopian tube(s) intrauterine insemination (IUI) with or without ovulation induction, is indicated. When these treatments fail, in cases, women over the age of 39 years, in women with IID, in men or women who harbor antisperm antibodies in significant concentrations and in cases associated with tubal abnormalities, in vitro fertilization (IVF) is needed. All cases of intractable, moderate or severe male infertility call for injecting sperm directly into the egg to achieve forced fertilization (intracytoplasmic sperm injection-ICSI).
It is an indisputable fact that most causes of infertility can be diagnosed and it is a great pity that the diagnosis of “unexplained infertility” is often used as an excuse for not having performed a full and detailed evaluation of the problem. Couples should not simply accept a diagnosis of “unexplained infertility” at face value since treatment is most likely to be successful when the specific cause of the problem can be fully identified

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
• Ovarian Stimulation for IVF using GnRH Antagonists: Comparing the Agonist/Antagonist Conversion Protocol.(A/ACP) With the “Conventional” Antagonist Approach
• 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.
• The “Biological Clock” and how it should Influence the Selection and Design of Ovarian Stimulation Protocols for 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?
• Blastocyst Embryo Transfers Should be the Standard of Care in IVF
• 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
• Treating Out-of-State and Out-of-Country Patients at Sher-IVF in Las Vegas:
• 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
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.

reply
kirti

thankyou doc. also I wanted to add is I have been taking epilex since age of 15 and now for last 5 years on tegritol 200mg. also on thyronorm 100mcg. I had informed my gyn about it. she said tegritol will not have any impact on fertility.. is it true?

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Dr. Geoffrey Sher

The Tegretol does not really concern me much. I am more concerned that you are taking synthroid and thus have underlying hypothyroidism and most hypothyroidism in women is autoimmune in origin. Considering that in my opinion, 50% of women with thyroid autoimmune disease also have an immunologic implantation dysfunction, this is what needs to be assessed and if present…addressed.

Between 2% and 5% of women of the childbearing age have reduced thyroid hormone activity (hypothyroidism). Women with hypothyroidism often manifest with reproductive failure i.e. infertility, unexplained (often repeated) IVF failure, or recurrent pregnancy loss (RPL). The condition is 5-10 times more common in women than in men. In most cases hypothyroidism is caused by damage to the thyroid gland resulting from of thyroid autoimmunity (Hashimoto’s disease) caused by damage done to the thyroid gland by antithyroglobulin and antimicrosomal auto-antibodies.
The increased prevalence of hypothyroidism and thyroid autoimmunity (TAI) in women is likely the result of a combination of genetic factors, estrogen-related effects and chromosome X abnormalities. This having been said, there is significantly increased incidence of thyroid antibodies in non-pregnant women with a history of infertility and recurrent pregnancy loss and thyroid antibodies can be present asymptomatically in women without them manifesting with overt clinical or endocrinologic evidence of thyroid disease. In addition, these antibodies may persist in women who have suffered from hyper- or hypothyroidism even after normalization of their thyroid function by appropriate pharmacological treatment. The manifestations of reproductive dysfunction thus seem to be linked more to the presence of thyroid autoimmunity (TAI) than to clinical existence of hypothyroidism and treatment of the latter does not routinely result in a subsequent improvement in reproductive performance.
It follows, that if antithyroid autoantibodies are associated with reproductive dysfunction they may serve as useful markers for predicting poor outcome in patients undergoing assisted reproductive technologies.
Some years back, I reported on the fact that 47% of women who harbor thyroid autoantibodies, regardless of the absence or presence of clinical hypothyroidism, have activated uterine natural killer cells (NKa) cells and cytotoxic lymphocytes (CTL) and that such women often present with reproductive dysfunction. We demonstrated that appropriate immunotherapy with IVIG or intralipid (IL) and steroids, subsequently often results in a significant improvement in reproductive performance in such cases.
The fact that almost 50% of women who harbor antithyroid antibodies do not have activated CTL/NK cells suggests that it is NOT the antithyroid antibodies themselves that cause reproductive dysfunction. The activation of CTL and NK cells that occurs in half of the cases with TAI is probably an epiphenomenon with the associated reproductive dysfunction being due to CTL/NK cell activation that damages the early “root system” (trophoblast) of the implanting embryo. We have shown that treatment of those women who have thyroid antibodies + NKa/CTL using IL/steroids, improves subsequent reproductive performance while women with thyroid antibodies who do not harbor NKa/CTL do not require or benefit from such treatment.

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
• Ovarian Stimulation for IVF using GnRH Antagonists: Comparing the Agonist/Antagonist Conversion Protocol.(A/ACP) With the “Conventional” Antagonist Approach
• 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.
• 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!
• Treating Out-of-State and Out-of-Country Patients at Sher-IVF in Las Vegas:
• 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.

reply
vishu

Hello sir,

Good evening.. This is vishu. We are staying in chennai, India. We got married 2 and half years ago. we are going under treatment for a fertility clinic from the past 1 year. Doctor find that, My left ovary is not visible and right ovary also small. We have tried first ivf in june with my eggs, and it’s first failure.
We have tried second ivf with donor eggs and it got failed and the embryo(5days) was not impalnted .
Doctor is telling my embryo is not in good shape.. i.e. 777 shape. but it’s not a factor, i am aged 28 and my weight is 70kg. we have tried the third ivf with donor egg and we are waiting for result. By next week we will get result. we have spent lot of money for IVF and we are loosing our hopes. Could you please suggest me what is the problem with me. Can’t we identify why the embryo didnt implant ?.. and was there any tests to find out that. please suggest us.

reply
Dr. Geoffrey Sher

I suggest you wait for the outcome of your last attempt. If it is unsuccessful, then perhaps we should re-connect.

Geoff Sher

reply
Bri

Hi Dr. Sher,
After 3 failed FET’s this year, all things look normal, etc, I’m assuming to have IId, some kind of implantation disorder. I’ve gotten low hcg levels, like 5 and 29, so they’re trying to implant, but don’t. What are your thoughts on the endometrial receptability array (ERA) test? Is it worth it? I’m just worried I have to do multiple biopsies and it still might not even work.

reply
Dr. Geoffrey Sher

Frankly, I do not have confidence in the relia=bility or validity or ERA.

Feel free to 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.

Geoff Sher

reply
Jem

Dear Dr Sher, I have been trying to have a baby with my husband for the past 18 months. We were in a long distance relationship for the first two attempts to get me pregnant but both times I got pregnant on our first cycle of trying. The first time I got pregnant in April 2015, I had a missed miscarriage at 7 weeks which wasn’t detected until an ultrasound scan at 11 weeks. I had an emergency D&C when I started bleeding heavily. The second attempt to get pregnant was four months later and that was a chemical pregnancy that ended a week after a positive HPT. The third attempt occurred 6 months later and again I got pregnant straight away and that too ended in a missed miscarriage where the embryo did not develop beyond 6 weeks 1 day and I had a D&C at 11 weeks. That was in July 2016 and since then my husband and I have been living together and having unprotected sex on an almost daily basis and I have not become pregnant again. Each month I have felt like I might be pregnant but the signs have faded away after a week or so and I have not had a positive pregnancy test. My periods since the miscarriage have been light but they have been regular every 25-28 days and an ovulation kit suggests that I have been ovulating each month. I am 35 now and my husband is 47. He already has 4 children from previous relationships in the past. I have never tried to have children with anyone else before him. I had some thrombophilia testing and an ultrasound of my reproductive organs done at the start of this year and everything came back normal. I am increasingly wondering if this is an immune issue with me or me and my husband together. It is really distressing me especially as now I don’t seem able to even get pregnant. We don’t have the money to pay for all the possible tests we would like to have but I wondered if based on my history you think there are one or two tests that would specifically be worth having here.
Thank you

reply
Dr. Geoffrey Sher

When it comes to reproduction, humans are the poorest performers of all mammals. In fact we are so inefficient that up to 75% of fertilized eggs do not produce live births, and up to 30% of pregnancies end up being lost within 10 weeks of conception (in the first trimester). RPL is defined as two (2) or more failed pregnancies. Less than 5% of women will experience two (2) consecutive miscarriages, and only 1% experience three or more.
Pregnancy loss can be classified by the stage of pregnancy when the loss occurs:
• Early pregnancy loss (first trimester)
• Late pregnancy loss (after the first trimester)
• Occult “hidden” and not clinically recognized, (chemical) pregnancy loss (occurs prior to ultrasound confirmation of pregnancy)
• Early pregnancy losses usually occur sporadically (are not repetitive).
In more than 70% of cases the loss is due to embryo aneuploidy (where there are more or less than the normal quota of 46 chromosomes). Conversely, repeated losses (RPL), with isolated exceptions where the cause is structural (e.g., unbalanced translocations), are seldom attributable to numerical chromosomal abnormalities (aneuploidy). In fact, the vast majority of cases of RPL are attributable to non-chromosomal causes such as anatomical uterine abnormalities or Immunologic Implantation Dysfunction (IID).
Since most sporadic early pregnancy losses are induced by chromosomal factors and thus are non-repetitive, having had a single miscarriage the likelihood of a second one occurring is no greater than average. However, once having had two losses the chance of a third one occurring is double (35-40%) and after having had three losses the chance of a fourth miscarriage increases to about 60%. The reason for this is that the more miscarriages a woman has, the greater is the likelihood of this being due to a non-chromosomal (repetitive) cause such as IID. It follows that if numerical chromosomal analysis (karyotyping) of embryonic/fetal products derived from a miscarriage tests karyotypically normal, then by a process of elimination, there would be a strong likelihood of a miscarriage repeating in subsequent pregnancies and one would not have to wait for the disaster to recur before taking action. This is precisely why we strongly advocate that all miscarriage specimens be karyotyped.
There is however one caveat to be taken into consideration. That is that the laboratory performing the karyotyping might unwittingly be testing the mother’s cells rather than that of the conceptus. That is why it is not possible to confidently exclude aneuploidy in cases where karyotyping of products suggests a “chromosomally normal” (euploid) female.
Late pregnancy losses (occurring after completion of the 1st trimester/12th week) occur far less frequently (1%) than early pregnancy losses. They are most commonly due to anatomical abnormalities of the uterus and/or cervix. Weakness of the neck of the cervix rendering it able to act as an effective valve that retains the pregnancy (i.e., cervical incompetence) is in fact one of the commonest causes of late pregnancy loss. So also are developmental (congenital) abnormalities of the uterus (e.g., a uterine septum) and uterine fibroid tumors. In some cases intrauterine growth retardation, premature separation of the placenta (placental abruption), premature rupture of the membranes and premature labor can also causes of late pregnancy loss.
Much progress has been made in understanding the mechanisms involved in RPL. There are two broad categories:
1. Problems involving the uterine environment in which a normal embryo is prohibited from properly implanting and developing. Possible causes include:
• Inadequate thickening of the uterine lining
• Irregularity in the contour of the uterine cavity (polyps, fibroid tumors in the uterine wall, intra-uterine scarring and adenomyosis)
• Hormonal imbalances (progesterone deficiency or luteal phase defects). This most commonly results in occult RPL.
• Deficient blood flow to the uterine lining (thin uterine lining).
• Immunologic implantation dysfunction (IID). A major cause of RPL. Plays a role in 75% of cases where chromosomally normal preimplantation embryos fail to implant.
• Interference of blood supply to the developing conceptus can occur due to a hereditary clotting disorder known as Thrombophilia.
2. Genetic and/or structural chromosomal abnormality of the embryo.Genetic abnormalities are rare causes of RPL. Structural chromosomal abnormalities are slightly more common but are also occur infrequently (1%). These are referred to as unbalanced translocation and they result from part of one chromosome detaching and then fusing with another chromosome. Additionally, a number of studies suggest the existence of paternal (sperm derived) effect on human embryo quality and pregnancy outcome that are not reflected as a chromosomal abnormality. Damaged sperm DNA can have a negative impact on fetal development and present clinically as occult or early clinical miscarriage. The Sperm Chromatin Structure Assay (SCSA) which measures the same endpoints are newer and possibly improved methods for evaluating.

IMMUNOLOGIC IMPLANTATION DYSFUNCTION
Autoimmune IID: Here an immunologic reaction is produced by the individual to his/her body’s own cellular components. The most common antibodies that form in such situations are APA and antithyroid antibodies (ATA).
But it is only when specialized immune cells in the uterine lining, known as cytotoxic lymphocytes (CTL) and natural killer (NK) cells, become activated and start to release an excessive/disproportionate amount of TH-1 cytokines that attack the root system of the embryo, that implantation potential is jeopardized. Diagnosis of such activation requires highly specialized blood test for cytokine activity that can only be performed by a handful of reproductive immunology reference laboratories in the United States.
Alloimmune IID, i.e., where antibodies are formed against antigens derived from another member of the same species, is believed to be a relatively common immunologic cause of recurrent pregnancy loss.
Autoimmune IID is often genetically transmitted. Thus it should not be surprising to learn that it is more likely to exist in women who have a family (or personal) history of primary autoimmune diseases such as lupus erythematosus (LE), scleroderma or autoimmune hypothyroidism (Hashimoto’s disease), autoimmune hyperthyroidism (Grave’s disease), rheumatoid arthritis, etc. Reactionary (secondary) autoimmunity can occur in conjunction with any medical condition associated with widespread tissue damage. One such gynecologic condition is endometriosis. Since autoimmune IID is usually associated with activated NK and T-cells from the outset, it usually results in such very early destruction of the embryo’s root system that the patient does not even recognize that she is pregnant. Accordingly the condition usually presents as “unexplained infertility” or “unexplained IVF failure” rather than as a miscarriage.

Alloimmune IID, on the other hand, usually starts off presenting as unexplained miscarriages (often manifesting as RPL). Over time as NK/T cell activation builds and eventually becomes permanently established the patient often goes from RPL to “infertility” due to failed implantation. RPL is more commonly the consequence of alloimmune rather than autoimmune implantation dysfunction.
However, regardless, of whether miscarriage is due to autoimmune or alloimmune implantation dysfunction the final blow to the pregnancy is the result of activated NK cells and CTL in the uterine lining that damage the developing embryo’s “root system” (trophoblast) so that it can no longer sustain the growing conceptus. This having been said, it is important to note that autoimmune IID is readily amenable to reversal through timely, appropriately administered, selective immunotherapy, and alloimmune IID is not. It is much more difficult to treat successfully, even with the use of immunotherapy. In fact, in some cases the only solution will be to revert to selective immunotherapy plus using donor sperm (provided there is no “match” between the donor’s DQa profile and that of the female recipient) or alternatively to resort to gestational surrogacy.
DIAGNOSING THE CAUSE OF RPL
In the past, women who miscarried were not evaluated thoroughly until they had lost several pregnancies in a row. This was because sporadic miscarriages are most commonly the result of embryo numerical chromosomal irregularities (aneuploidy) and thus not treatable. However, a consecutive series of miscarriages points to a repetitive cause that is non-chromosomal and is potentially remediable. Since RPL is most commonly due to a uterine pathology or immunologic causes that are potentially treatable, it follows that early chromosomal evaluation of products of conception could point to a potentially treatable situation. Thus I strongly recommend that such testing be done in most cases of miscarriage. Doing so will avoid a great deal of unnecessary heartache for many patients.
Establishing the correct diagnosis is the first step toward determining effective treatment for couples with RPL. It results from a problem within the pregnancy itself or within the uterine environment where the pregnancy implants and grows. Diagnostic tests useful in identifying individuals at greater risk for a problem within the pregnancy itself include:

• Karyotyping (chromosome analysis) both prospective parents
• Assessment of the karyotype of products of conception derived from previous miscarriage specimens
• Ultrasound examination of the uterine cavity after sterile water is injected or sonohysterogram, fluid ultrasound, etc.)
• Hysterosalpingogram (dye X-ray test)
• Hysteroscopic evaluation of the uterine cavity
• Full hormonal evaluation (estrogen, progesterone, adrenal steroid hormones, thyroid hormones, FSH/LH, etc.)
• Immunologic testing to include:
a) Antiphospholipid antibody (APA) panel
b) Antinuclear antibody (ANA) panel
c) Antithyroid antibody panel (i.e., antithyroglobulin and antimicrosomal antibodies)
d) Reproductive immunophenotype
e) Natural killer cell activity (NKa) assay (i.e., K562 target cell test)
f) Alloimmune testing of both the male and female partners
TREATMENT OF RPL
Treatment for Anatomic Abnormalities of the Uterus: This involves restoration through removal of local lesions such as fibroids, scar tissue, and endometrial polyps or timely insertion of a cervical cerclage (a stitch placed around the neck of the weakened cervix) or the excision of a uterine septum when indicated.
Treatment of Thin Uterine Lining: A thin uterine lining has been shown to correlate with compromised pregnancy outcome. Often this will be associated with reduced blood flow to the endometrium. Such decreased blood flow to the uterus can be improved through treatment with sildenafil and possibly aspirin.
Sildenafil (Viagra) Therapy. Viagra has been used successfully to increase uterine blood flow. However, to be effective it must be administered starting as soon as the period stops up until the day of ovulation and it must be administered vaginally (not orally). Viagra in the form of vaginal suppositories given in the dosage of 25 mg four times a day has been shown to increase uterine blood flow as well as thickness of the uterine lining. To date, we have seen significant improvement of the thickness of the uterine lining in about 70% of women treated. Successful pregnancy resulted in 42% of women who responded to the Viagra. It should be remembered that most of these women had previously experienced repeated IVF failures.

Use of Aspirin: This is an anti-prostaglandin that improves blood flow to the endometrium. It is administered at a dosage of 81 mg orally, daily from the beginning of the cycle until ovulation.
Treating Immunologic Implantation Dysfunction with Selective Immunotherapy: Modalities such as IL/IVIg, heparinoids (Lovenox/Clexane), and corticosteroids (dexamethasone, prednisone, prednisolone) can be used in select cases depending on autoimmune or alloimmune dysfunction.
The Use of IVF in the Treatment of RPL
In the following circumstances, IVF is the preferred option:
1. When in addition to a history of RPL, another standard indication for IVF (e.g., tubal factor, endometriosis, and male factor infertility) is superimposed.
2. In cases where selective immunotherapy is needed to treat an immunologic implantation dysfunction.
The reason for IVF being a preferred approach in such cases is that in order to be effective, the immunotherapy needs to be initiated well before spontaneous or induced ovulation. Given the fact that the anticipated birthrate per cycle of COS with or without IUI is at best about 15%, it follows that short of IVF, to have even a reasonable chance of a live birth, most women with immunologic causes of RPL would need to undergo immunotherapy repeatedly, over consecutive cycles. Conversely, with IVF, the chance of a successful outcome in a single cycle of treatment is several times greater and, because of the attenuated and concentrated time period required for treatment, IVF is far safer and thus represents a more practicable alternative
Since embryo aneuploidy is a common cause of miscarriage, the use of preimplantation genetic diagnosis (PGD), with tests such as CGH, can provide a valuable diagnostic and therapeutic advantage in cases of RPL. PGD requires IVF to provide access to embryos for testing.
There are a few cases of intractable alloimmune dysfunction due to absolute DQ alpha matching where Gestational Surrogacy or use of donor sperm could represent the only viable recourse, other than abandoning treatment altogether and/or resorting to adoption. Other non-immunologic factors such as an intractably thin uterine lining or severe uterine pathology might also warrant that last resort consideration be given to gestational surrogacy.
The good news is that if a couple with RPL is open to all of the diagnostic and treatment options referred to above, a live birthrate of 70%–80% is ultimately achievable.

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 Approach
• 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.
• 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
• Optimizing Response to Ovarian Stimulation in Women who Have Compromised Ovarian Response to Ovarian Stimulation in Women who
• 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
• Why did my IVF Fail
• Premature Birth and 2nd Trimester Recurrent Pregnancy Loss (RPL)
• Hereditary Clotting Defects (Thrombophilia)
• Blastocyst Embryo Transfers Done 5-6 Days Following Fertilization are Fast Replacing Earlier day 2-3 Transfers of Cleaved Embryos.
• Frozen Embryo Transfer (FET) versus “Fresh” ET: How to Make the Decision
• 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
• Treating Out-of-State and Out-of-Country Patients at Sher-IVF in Las Vegas:
• 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

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.

reply
Jem

Thank you very much for your detailed response. Based on your answer, I am feeling it is quite possible that I have the autoimmune or alloimmune issues you discussed. Am I right in thinking that if this is an autoimmune issue then it would occur regardless of who the father was because my own body is attacking the embryo?…. however if this was an alloimmune issue then it is possible this issue would only arise with my husband and not necessarily if the father was someone else with different genetics?

reply
Yvette

Dr.Sher, I was recently diagnosed with RIP (reproductive immunology). I am on my 8th failed IUI with no explanation as to why it has not taken. This is my first cycle on Clomid and I did two previous cycles with Femera. I responded well to Clomid. My question is , my doctor explained how to treat and balance my NK cells but also did an additional blood text to see how my body responds to IL or IVIG and the results came back saying that the treatment I need is IVIG and not IL. I was reading here on your blog that you think either treatment is effective? I am just in shock on how much these IVIG treatments will cost and if they are effective. I am currently 2 days post final IUI with an IL treatment and a bit lost on what to do next? Would you even recommend to go forward with IVF without “treating” this RIP?

Any input would be greatly appreciated,

Thank you,
Yvette

reply
Dr. Geoffrey Sher

Hi Yvette,

Absolutely, both IL and IVIG will be equallly effective. Interpretation of the tests your doctor referring to that makes him/her believe IVIG to be bertter can be deceptive…Besides, I would argue against this treatment in association with anything other than IVF. Please see the articcles below……I think we should talk.

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 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 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!
• 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–
• 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
• Intrauterine Insemination (IUI): Who Needs it & who Does Not: Pro’s & Con’s!
• Micro-IVF: Often Preferable to Ovarian Stimulation with or Without IUI

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.

reply
Alex

Hi Dr. Sher,

You mention that several Autoimmune implantation dysfunctons with activated Natural Killers cells can come with such things like Rheumatoid arthritis , hypothyroid etc….but is hyperthyroid (graves disease) which is what my friend has…. also linked often with “activated” natural killer cells in your experience? Her RE doesn’t believe in autoimmune issues and said if her thyroid is under control with meds she is fine. Her uterus is fine they say, she has genetically sound embryos and has tried one transfer but it has failed. They have been trying to get pregnant for 6 years with not one pregnancy. She only has 2 genetically sound embryos left to transfer in a few weeks. Should she get tested for activated killer cells before her last attempted transfer as she cant afford any more cycles.

reply
Dr. Geoffrey Sher

Indeed, in my opinion, since hyperthyroidism is also often an autoimmune condition , it can likewise be associated with an immunologic implantation dysfunction (IID) linked to activated uterine natural killer cells (NKa) and if so would require intralipid/steroid regulation.

Based upon what you have stated, I would not be at all surprised if an IID is involved here.

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
• 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
• Why did my IVF Fail
• 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!
• 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.

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.

reply
Nina Nguyen

Hi Dr. Sher,
I had a D&C surgery in 2013 at 16 weeks plus. Since then, I have been tried to conceive but no luck. I had a couple IUI done at the fertility clinic in MD, but all of them failed. My doctor said my case is unexplained infertility because they did all the tests on me (HSG) and my husband, we are normal. My uterine cavity is normal according to HSG test. However, my uterine lining is pretty thin according to the ultrasound on day 10, it is 5.9mm for first cycle then 6.7 mm second IUI and this past IUI is 6.49mm. I was wondering if the thin lining is the root cause of my infertility. I was given Estrace and Progesterone to improve the thin uterus lining but still unsuccessful. All those cycles, I took Clomid and ovidrel trigger shot. Now I would like to move on natural cycle IVF but not sure about the outcome. In your opinion, if I proceed to natural cycle IVF, what is the success rate for my case and my age (39 years old). Have you had any patients with the same case as me and got pregnant successfully after a D&C at 2nd trimester? Do you think Viagra will increase the lining in my case? Do RE often prescribe Viagra in fertility clinics? I read your blog about Viagra improving thin lining and I am really hoping if I take Viagra, it will work for me as well. Your response is greatly appreciated. Thank you so much.

reply
Dr. Geoffrey Sher

I have asuspicion that your thin lining was due to consecutive clomiphene stimulations. This is a typical consequence of doing >3 clomiphene cycles without at least a 1 month break after the 3rd. It happens because one of the components of clomiphene has a long half-life and builds up in the system. No one (in my opinion) should do >3 clomiphene cycles in a row without a break….see below.

Second, I strongly advise against natural cycle IVF. The success rate is dismal and it is a counter-productive approach in older women…especiall those who have diminished ovarian reserve. In my opinion, you need a modified, long pituitary down-regulation protocol. I would use an agonist/antagonist conversion protocol with human growth hormone (HGH) augmentation and would recommend Staggered IVF with embryo banking of PGS (next generation gene sequencing)-normal blastocysts.

Geoffrey Sher MD
Clomiphene (syn; Clomid , Serophene) is by far the most widely prescribed agent for the induction of human ovulation for women who do not ovulate, those with dysfunctional ovulation and women with ”unexplained” infertility. When used in young women (who have adequate ovarian reserve) with these problems the viable pregnancy rate is reported as being between 6% and 10% per cycle of treatment. Aside from conventional ovulation induction, clomiphene has been used in preparing women for intrauterine insemination and even for IVF. I personally rarely prescribe clomiphene because across the board, success rates are significantly lower than when gonadotropin therapy is used. The main reasons for clomiphene’s popularity is its low cost, simplicity of use and the low risk of dangerous complications such as severe ovarian hyperstimulation syndrome (OHSS).
Clomiphene treatment can be initiated at a dose of 50 mg (orally) daily for 5 days but it can be increased to as much as 200mg per day, starting on cycle 2, 3, 4, or 5. A spontaneous LH surge will usually follow within about 8-9 days of the last 50mg dosage. In some cases, 10,000U of hCG can be given as a trigger when there is at least one ovarian follicle of 18-20 mm in size. Routinely using the hCG trigger does tend to decrease pregnancy potential.
Clomiphene works by inducing ovulation through its “antiestrogen effect” which, by blocking estrogen receptors in an area of the brain known as the hypothalamus, tricks the brain into “thinking” that estrogen levels are low. In response, the hypothalamus prompts the pituitary gland to release an exaggerated amount of follicle-stimulating hormone (FSH), which in turn stimulates the growth and development of ovarian follicles, ultimately resulting in a surge in the release of pituitary LH. About 38-42 hours later, ovulation occurs from one or more of the larger follicles. As the follicles grow, they release more and more estrogen into the bloodstream, thus closing the feedback circle that the hypothalamus initiated in response to the anti-estrogen properties of Clomiphene.
There are several factors that need to be considered carefully before deciding to prescribe clomiphene to any woman:
• Clomiphene citrate therapy is less effective than gonadotropin therapy and its efficacy declines with advancing age: Many infertile couples undergoing ovulation induction believe that the success rate using clomiphene citrate is equivalent to what we see in fertile couples trying to get pregnant on their own and to what is encountered when gonadotropins (Menopur/Follistim/Gonal-F and Puregon) are used. This is not the case. The truth is that the rate of conception with clomiphene therapy is actually about 30% lower than the natural fertility rate for normally ovulating women, and about 25% lower than when gonadotropin stimulation is used for ovarian stimulation in similar patients. Moreover, the discrepancy is further magnified with advancing maternal age, where in women under 35 years, the pregnancy rate with clomiphene treatment is about 10% per cycle, about 5% between 35 and 40 years and <2% for women in their early to mid-forties.
• Clomiphene use should ideally be confined to younger women: Ideally the use of clomiphene should in my opinion be restricted to younger women (under 35 years) who have normal “ovarian reserve” (as assessed by basal blood FSH, and antimullerian hormone (AMH) levels). These are the women who are most likely to respond by producing multiple follicles. It is necessary that at least 3 sizeable follicles (>15mm) develop on clomiphene treatment, in order to override the “anti-estrogenic” effects of this drug and so insure adequate cervical mucus production as well as the development of a receptive endometrium.
• Clomiphene should usually not be administered for more than 3 consecutive (back-to- back) cycles: If used back-to-back for more than 3 consecutive cycles, clomiphene is not only ineffective, but actually starts to function as a “relative” contraceptive! This is often is a shocking revelation to many women. Clomiphene’s anti-estrogenic effect is not confined to the hypothalamus. Any cells that have a high concentration of estrogen receptors will also be so affected. Needless to say, the cervical glands (that produce estrogenic mucus to facilitate sperm transport and the endometrial lining (endometrium) that thickens under the effect of estrogen are also highly vulnerable to a buildup of antiestrogen effects over successive back-to back cycles of clomiphene therapy. This why with >3 consecutive back-to back clomiphene cycles cervical mucus tends to thicken and dry up and the endometrium will thin, seriously reducing the likelihood of success. These anti-estrogenic manifestations require that following 3 back-to back clomiphene cycles of stimulation there be at least 1 resting (non-clomiphene treated) cycle, before doing a 4th cycle.
• Clomiphene should not be used in older women or in women who have diminished ovarian reserve (DOR): With clomiphene stimulation, the release of pituitary FSH is always accompanied by the concomitant release of Luteinizing Hormone (LH). LH causes the ovary to produce male hormone (androgens) and testosterone. The production by the ovaries of a modest amount of testosterone would not present a problem. However, an excessive production of ovarian testosterone prejudices egg development and thus ultimately compromises embryo competency. Older women and women with DOR are the most vulnerable because they tend to have overgrowth of ovarian connective tissue (stroma/theca) which is the site where androgens are produced. The concentration of androgens is always much higher at the site of production (the ovaries) than in the peripheral blood (a dilution effect). Thus in older women and those with DOR, there will be excessive ovarian androgens that can compromise egg quality and thus ultimately reduce the chance of having a baby. The older the woman and/or the more severe the DOR, the greater this adverse effect is likely to be.
• “Trapped” ovulation (LUF-Syndrome): About 20% of clomiphene cycles are associated with “trapped” ovulation (Luteinized Unruptured Follicle (LUF) Syndrome). This means that in spite of hormone changes suggesting that ovulation has occurred, the egg remains trapped in the ovary. Obviously this is not condusive to the establishment of a successful pregnancy.
• Endometriosis is a “relative contraindication” to the use of clomiphene: Women with endometriosis (regardless of its severity) have” toxic factors” in their pelvic peritoneal fluid. Eggs, as they pass from the ovaries to the Fallopian tubes to reach the awaiting sperm, become exposed to these “toxins” which renders the egg envelopment (zona pellucida) resistant to sperm penetration. This reduces fertilization potential by a factor of at least 3 or 4. This means that if, in the absence of endometriosis, an egg has a 15% chance of being fertilized and thereupon resulting in a baby, that same egg, in a woman with endometriosis would have no more than a 5% chance. Thus, if the overall chance of a having a baby per year of actively trying is about 12% then the chance in a woman with mild endometriosis (of the same age) would probably be no more than 3-4%. This serves to explain why normally ovulating women with endometriosis and patent Fallopian tubes do not benefit significantly from intrauterine insemination, with or without the use of fertility drugs, or from surgery to remove endometriotic lesions (since many endometriotic deposits are non-pigmented, thus invisible to the naked eye and cannot be removed surgically). Only IVF improves the chance of a baby per month of trying. Simply put…if a normally ovulating woman who has mild to moderate endometriosis conceives following IUI, surgery, or the use of fertility drugs, it is probably in spite of (rather than due) to such treatment.
• Women with long gaps between menstruation are often not ideal candidates for clomiphene: Women who consistently have >45 days between their periods will not respond well to clomiphene induction of ovulation and are better off going directly to injectable gonadotropins.
• Multiple pregnancy: The incidence of multiple pregnancies with clomiphene induction of ovulation is about 5%. This is much lower than the 25% rate encountered when gonadotropins are given to women with absent or dysfunctional ovulation.
Clomiphene therapy is often used as a first line approach to inducing ovulation in women with irregular or absent ovulation such as in women with polycystic ovarian syndrome (PCOS). Its use in my opinion is best confined to women who menstruate/ovulate irregularly (but who bleed at least every 45 days), younger women, women who do not have tubal disease or endometriosis, women under 40 years of age (preferably <35Y), and women who do not have DOR . It should also be avoided when there is co-existing male factor infertility. If pregnancy fails to occur after 3 consecutive cycles of clomiphene therapy, then in my opinion, it is time to move on to gonadotropin therapy, combined with IUI or IVF/ICSI depending on the underlying cause of the infertility.

Please visit my new Blog on this very site, http://www.DrGeoffreySherIVF.com, find the “search bar” and type in the titles of any/all of the articles listed below, one by one. “Click” and you will immediately be taken to those you select. Please also take the time to post any questions or comments with the full expectation that I will (as always) respond promptly
• Controlled Ovarian Stimulation (COS) for IVF: Selecting the ideal protocol
• Ovarian Stimulation for IVF using GnRH Antagonists: Comparing the Agonist/Antagonist Conversion Protocol.(A/ACP) With the“Conventional” Antagonist Aproach
• IVF: Factors Affecting Egg/Embryo “competency” during Controlled Ovarian Stimulation(COS)
• Anti Mullerian Hormone (AMH) Measurement to Assess Ovarian Reserve and Design the Optimal Protocol for Controlled Ovarian Stimulation (COS) in IVF.
• The “Biological Clock” and how it should Influence the Selection and Design of Ovarian Stimulation Protocols for IVF.
• Diagnosing and Treating Infertility due to Diminished Ovarian Reserve (DOR)
• Human Growth Hormone Administration in IVF: Does it Enhances Egg/Embryo Quality and Outcome?
• The BCP: Does Launching a Cycle of Controlled Ovarian Stimulation (COS). Coming off the BCP Compromise Response?
• Frozen Embryo Transfer (FET): A Rational Approach to Hormonal Preparation and How new Methodology is Impacting IVF.
• Staggered IVF: An Excellent Option When. Advancing Age and Diminished Ovarian Reserve (DOR) Reduces IVF Success Rate
• Embryo Banking/Stockpiling: Slows the “Biological Clock” and offers a Selective Alternative to IVF-Egg Donation.
• Preimplantation Genetic Sampling (PGS) Using: Next Generation Gene Sequencing (NGS): Method of Choice.
• IVF Failure and Implantation Dysfunction: The Role of Endometrial Thickness, Uterine Pathology and Immunologic Factors
• Why did my IVF Fail
• Immunologic Implantation Dysfunction (IID) & Infertility (IID):PART 1-Background
• Immunologic Implantation Dysfunction (IID) & Infertility (IID):PART 2- Making a Diagnosis
• Immunologic Dysfunction (IID) & Infertility (IID):PART 3-Treatment
• Thyroid autoantibodies and Immunologic Implantation Dysfunction (IID)
• Immunologic Implantation Dysfunction: Importance of Meticulous Evaluation and Strategic Management:(Case Report)
• Natural Killer Cell Activation (NKa) and Immunologic Implantation Dysfunction in IVF: The Controversy!
• Traveling for IVF from Out of State/Country–
• A personalized, stepwise approach to IVF
• How Many Embryos should be transferred: A Critical Decision in IVF.
• The Role of Nutritional Supplements in Preparing for IVF
I invite you to call 702-699-7437 or 800-780-7437 or go online on this site and set up a one hour Skype consultation with me to discuss your case in detail.

I also suggest that you access the 4th edition of my book ,”In Vitro Fertilization, the ART of Making Babies”. It is available as a down-load through http://www.Amazon.com or from most bookstores and public libraries.

Geoff Sher

reply
Carmela

Hello Dr Sher,

I had a FET last year and had a miscarriage mostly likely due to embryo quality. We took a break and I had another FET #2 done for Jan/Feb cycle. But my lining was not great, it was irregular and so we decided to cancel the cycle.

After the cancelled FET he did a sonohysterogram with saline which there is fibroid that is bulging into the uterine cavity but the good news is I have no polyps, no scarring, and no fibroids inside the uterus except for the sub mucous fibroid. But the doctor wants me to have a hysteroscopy and a possible D&C. The size is about 8×5.

In your professional opinion, do you think this type of fibroid can cause lining and implantation issues? And would you recommend me to get the fibroid removed or shaved off?

Thank you for taking the time reading and replying back

reply
Dr. Geoffrey Sher

Absolutely…In my opinion fibroids that protrude into or encroach on the uterine cavity should be removed prior to ET.

The uterus is composed of a thick layer of smooth muscle (myometrium) surrounding thin lining (the endometrium) into which the embryo implants and which serves to protect and nourish a growing pregnancy. Approximately 20-40% of all reproductive age women will develop benign growths of the myometrium, referred to as fibroid tumors (leimomyata). These tumors are rarely malignant (see below). They can be located in the wall of the uterus (intramural), on the outside of the uterus (subserosal), within the uterine cavity (submucosal), on a thin stalk (pedunculated) or a combination of the above. Estrogen causes them to grow. African and African American women seem to have a much higher incidence of fibroid tumors. In fact, while fibroids are very rarely detected in young Caucasian women, it is quite common to find these tumors in twenty to thirty year old African and African American women.

Fibroid tumors, even large ones, can occur without producing any symptoms at all. However they can also cause a variety of symptoms depending on their size, location and the absence or presence of complications such as tortion (twisting) or degeneration (such as might occur when a fibroid grows so fast that it starts running out of its blood supply). The most common symptoms are heavy cyclical menstrual bleeding (menorrhagia) accompanied by menstrual pain (dysmenorrhea). Sometimes, especially when a fibroid protrudes into the uterine cavity, it can cause erosion of the endometrial lining and produce irregular or continuous bleeding (menomettrorhagia).

Sustained non-menstrual pelvic pain may point to tortion of a pedunculated fibroid that is attached to the inner or outer wall of the uterus, or to degeneration, Other possible symptoms include pain with deep penetration during intercourse deep dyspareunia), bladder irritability, rectal pressure, constipation and painful bowel movements (dyschezia).

For the most part, only those fibroids that impinge upon the uterine (endometrial) cavity (submucosal) affect fertility. Exceptions include large fibroids in the muscle wall of the uterus (intramural) that can block the openings of the fallopian tubes as they enter the uterus, and where multiple fibroids cause abnormal uterine contraction patterns.

Surgery to remove fibroids (myomectomy) can also affect fertility in several ways. If the endometrial cavity is entered during the surgery, there is a possibility of post adhesions forming within the uterine cavity. This should always be checked for through the performance of a hysteroscopy or through a fluid ultrasound (sonohysterogram), prior to beginning fertility treatment. Because myomectomy can be bloody, there is a high likelihood of post-operative abdominal adhesion formation, which could bind down or encase the ovaries, preventing the release of the eggs or block the ends of the fallopian tubes. For this reason it is important that only accomplished surgeons, who are familiar with techniques to limit blood loss and prevent adhesion formation, perform myomectomies.

In some cases multiple uterine fibroids may so deprive the uterine lining (endometrium) of blood flow, that the delivery of estrogen to the endometrium is curtailed to the point that the lining cannot thicken sufficient to support a pregnancy. This can result in early 1st trimester (prior to the 13th week of pregnancy) miscarriages. Large or multiple fibroids, by curtailing the ability of the uterus to stretch in order to accommodate the spatial needs of a rapidly growing pregnancy, may precipitate 2nd trimester (beyond the 13th week) miscarriages and/or trigger the onset of premature labor.

Sizable fibroid tumors are usually easily identified by simple vaginal examination. However, even the smallest fibroid can be identified by transvaginal ultrasound. Sometimes it is difficult to tell if the fibroid is impinging on the uterine cavity. In such cases, a hysteroscopy (where a telescope like instrument, inserted via the vagina into the uterine cavity) or a sonohysterogram (where injected fluid, distends the uterine cavity allowing for examination of its inner configuration) can help distinguish between intramural and submucosal fibroids. Magnetic Resonance Imaging (MRI) can also be used to distinguish between fibroid tumors and another condition that also involves affects the uterine muscular wall, known as adenomyosis. This condition is characterized by endometrial growing deeply into the uterine wall.. Given the often-diffuse nature of adenomyosis, it can be very difficult to remove surgically. This contrasts with fibroid tumors, which are well defined and are usually easily removed.

Surgical Treatment: The mainstay for the treatment of fibroid tumors is surgical removal (myomectomy). Small, asymptomatic fibroids that do not impinge upon the endometrial cavity will usually not require treatment other than observation and vigilance. Large fibroids and submucosal fibroids should be removed prior to starting fertility treatments such as In Vitro Fertilization (IVF) in order to decrease the chance of implantation failure, miscarriage, pregnancy complications and premature labor. Intramural and subserosal fibroids are readily removable by laparoscopic resection or via an abdominal incision. The former allows for a more rapid convalescence and is ideal for the removal of small and accessible superficial fibroid tumors, while the latter approach is preferred for treating larger and less accessible fibroids.

Regardless of whether the laparoscopic or abdominal approach is employed, adequate closure of the uterine wall is essential in order to reduce the subsequent risk of uterine rupture during pregnancy or labor. This is one of the main arguments used against the use of laparoscopic removal of large, multiple or remotely situated fibroids. While laparoscopic myomectomy requires but a few days (at most) for post-operative convalescence, abdominal myomectomy usually requires 6-8 weeks of recovery time. When myomectomy necessitates or results in the uterine cavity being entered (purposefully or inadvertently), it should always be followed up with a “2nd look” hysteroscopy to rule out scar tissue formation, which occurs frequently in the presence of submucosal fibroids.

Uterine polyps (and in some cases, also submucosal fibroids), can often be removed hysteroscopically (through the vagina). This eliminates the need for abdominal surgery and greatly reduces the recovery time. Hysteroscopic surgery is only useful if the majority of the fibroid protrudes into the endometrial cavity, ensuring that the tumor defect will not be too large. This surgery is often done under laparoscopic guidance, to reduce the risk of uterine perforation. After hysteroscopic surgery it is often advisable to prescribe cyclical hormonal therapy for a few moths to encourage regeneration of the endometrial lining over the area of tumor defect and healing of the uterine muscle. A 2nd look hysteroscopy should be performed a few months later in all cases, to rule out scar tissue formation even if it means delaying or deferring the initiation of definitive fertility treatment.

Medical Treatment: The growth of fibroid tumors is estrogen-dependent. Thus when a woman enters the menopause and stops making female hormones, fibroids tend to shrink in size on their own. Conditions that mimic menopause can also reduce the size of fibroid tumors. The most common of theses treatment is with a medication such as lupreulide acetate (Lupron), which shut off the communication of the brain with the ovaries, preventing hormone production. However, this type of medication can only be taken for a limited period (usually 6 months) and once the medication is stopped the fibroids will usually regain their original size within a few months. The medication is therefore only a “temporary fix”; used mostly to decrease the size of large fibroids in order to make their ultimate surgical removal easier or to help a woman bridge the gap until spontaneous menopause sets in. For the majority of women there is no major benefit from Lupron therapy prior to surgery.

Embolization of Fibroid Tumors: Myomectomy always carries the small risk of that severe, uncontrollable intra-operative bleeding that although infrequent, could require the performance of a hysterectomy (complete removal of the uterus), as a life saving measure, might be required. Moreover, some women are poor surgical candidates for surgery. This is where a new procedure known as “embolization” comes in. Embolization is a procedure in which small particles are injected into the arteries of the uterus under radiological guidance to shut off the blood supply to the fibroids, in the hope that they will “shrink” and perhaps even, disappear.

Embolization is relatively new to the field of gynecology and little is known about its potential effects on future fertility. We are concerned that in the process of shutting off the blood supply to the uterus, it will permanently so reduce endometrial blood flow, as to compromise embryo implantation. For this reason, I do not currently recommend this therapy for women who still wish to conceive and carry a baby in their uterus. At present it seems best suited for symptomatic women who are finished with their childbearing or who are planning to use a gestational surrogate.

Malignant Change in Fibroid Tumors: Fibroids rarely undergo malignant change. The reported incidence is less than 1: 2000.. Fibroids usually grow very slowly (over a number of years). However, when growth occurs rapidly over a month or two, especially in older women who have large fibroids, it should raise the suspicion of this very rare but extremely serious complication.

Please visit my new Blog on this very site, http://www.DrGeoffreySherIVF.com, find the “search bar” and type in the titles of any/all of the articles listed below, one by one. “Click” and you will immediately be taken to those you select. Please also take the time to post any questions or comments with the full expectation that I will (as always) respond promptly.

• Controlled Ovarian Stimulation (COS) for IVF: Selecting the ideal protocol
• Ovarian Stimulation for IVF using GnRH Antagonists: Comparing the Agonist/Antagonist Conversion Protocol.(A/ACP) With the“Conventional” Antagonist Aproach
• IVF: Factors Affecting Egg/Embryo “competency” during Controlled Ovarian Stimulation(COS)
• Anti Mullerian Hormone (AMH) Measurement to Assess Ovarian Reserve and Design the Optimal Protocol for Controlled Ovarian Stimulation (COS) in IVF.
• The “Biological Clock” and how it should Influence the Selection and Design of Ovarian Stimulation Protocols for IVF.
• Diagnosing and Treating Infertility due to Diminished Ovarian Reserve (DOR)
• Human Growth Hormone Administration in IVF: Does it Enhances Egg/Embryo Quality and Outcome?
• The BCP: Does Launching a Cycle of Controlled Ovarian Stimulation (COS). Coming off the BCP Compromise Response?
• Frozen Embryo Transfer (FET): A Rational Approach to Hormonal Preparation and How new Methodology is Impacting IVF.
• Staggered IVF: An Excellent Option When. Advancing Age and Diminished Ovarian Reserve (DOR) Reduces IVF Success Rate
• 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

I invite you to call 702-699-7437 or 800-780-7437 or go online on this site and set up a one hour Skype consultation with me to discuss your case in detail.

I also suggest that you access the 4th edition of my book ,”In Vitro Fertilization, the ART of Making Babies”. It is available as a down-load through http://www.Amazon.com or from most bookstores and public libraries.

Geoff Sher

reply
Michelle

Hi Dr. Sher
I am currently attempting my 1st DE fet, third ivf cycle, first two were De fresh cycles and failures!
I obviously have implantation issues as I have never gotten a positive. Donor eggs of very high quality. I have xy dysgenesis so obviously cannot produce my own eggs.

Lining was 11 mm last cycle, I was taking oestrogen tabs x3 cyclogest x3 clexane steroids. I have high cd19+cd5 cells
This time I had a hysteroscopy and many polyps were discovered and removed, maybe due to years of hrt! I have also asked to change to gestone inj!
Is there anything else I could do, would you think I am on the right track? I am at a loss as to where to next!
Thank you

reply
Dr. Geoffrey Sher

Hi Michelle!

I would really require much more information to comment authoritaively. Something clearly is being overlooked in your case of unexplained IVF failure.

When confronted with “unexplained” IVF failures where morphologically good embryos were transferred, the question arises as to whether the problem is due to inherent egg/embryo “incompetence” (which usually equates with an irregular chromosomal configuration [aneuploidy]) or whether it is due to an implantation dysfunction. The younger the woman and the higher the quality of available embryos (preferably blastocysts), the less likely it is that the fault lies with embryo “incompetence” and the greater is the likelihood that it is due to underlying implantation dysfunction.
The most common causes of implantation dysfunction are:
a) A “thin uterine lining”
b) A uterus with surface lesions in the cavity (polyps, fibroids, scar tissue)
c) Immunologic implantation dysfunction (IID)
Implantation dysfunction (anatomical or immunologic) is a common cause of repeated “unexplained” IVF failure with good embryos. This is especially the case in young ovulating women who have normal ovarian reserve and have fertile partners. Failure to identify, typify, and address such issues is, in my opinion, an unfortunate and relatively common cause of repeated IVF failure in such women.

ADDITIONAL INFORMATION!
I urge you to access my new personal website at http://www.DrGeoffreySherIVF.com and from there, my new blog. When you get to the “home page” of the Blog, find the “search bar” and type in any of the articles below by title, “click” and you will immediately be taken to these. While on this blog, please take the opportunity to post any questions or comments with the full expectation that I will (as always) respond promptly.

• Controlled Ovarian Stimulation (COS) for IVF: Selecting the ideal protocol
• Ovarian Stimulation for IVF using GnRH Antagonists: Comparing the Agonist/Antagonist
• IVF Failure and Implantation Dysfunction: The Role of Endometrial Thickness, Uterine Pathology and Immunologic Factors
• Unexplained IVF Failure
• 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)
• Recurrent Pregnancy Loss (RPL): Why do I keep losing my Pregnancies?• Traveling for IVF from Out of State/Country–
• A personalized, stepwise approach to IVF at SIRM”; Parts 1 & 2 (posted March, 2012)
• The Role of Nutritional Supplements in Preparing for IVF
• Frozen Embryo Transfer (FET): What Does it Involve?
• Hereditary Clotting Defects (Thrombophilia)
• Staggered IVF: An Excellent Option When. Advancing Age and Diminished Ovarian Reserve (DOR) Reduces IVF Success Rate
• PGS-Biopsy for the Assessment of Embryo Numerical Chromosomal integrity (Ploidy): Should it be done on Day 3 or on Day 5-6 post fertilization?
• Launching Ovarian Stimulation with a BCP: How Does it Affect Response?
• Preimplantation Genetic Sampling (PGS) Using: Next Generation Gene Sequencing (NGS): Method of Choice.
• Male Factor Infertility

• IVF Egg Donation: A Comprehensive Overview

I invite you to call 702-699-7437 or 800-780-7437 and set up a one hour Skype consultation with me to discuss your case in detail.

I also suggest that you access the 4th edition of my book ,”In Vitro Fertilization, the ART of Making Babies”. It is available as a down-load through http://www.Amazon.com or from most bookstores and public libraries.

Geoff Sher

reply
Nichole Hallock

Hello Dr. Sher,

My husband and I have been dealing with infertility for just over 6 years now. I am 33 and my husband is 34. We have been under the care of an IVF clinic in Miami, FL for the past year and a half with still no desired results. After 3 failed IUIs and our second failed IVF FET using 2 excellent quality blastocysts per cycle we are really starting to lose hope. This past cycle my RE performed additional testing and confirmed activated NK cells, phospholipid antibodies and something else having to do with blood clotting. I was given an intralipid infusion 10 days prior to FET and also started 40mg of lovenox the day of FET. This was in addition to the estrogen patches, progesterone and baby aspirin. I have not been able to get a positive pregnancy test yet. I have one daughter who is now 10 years old. She was conceived naturally and prior to hypothyroidism. I am treated with synthroid daily and my TSH levels are less than 1.0. I truly believe that since then I have developed an implantation disorder but cannot get a straight answer from any doctors on if there is a correlation between the two situations. I did however have a chemical pregnancy 4 years ago and nothing since then. I read an article about a couple that you treated with a similar issue and the main difference in treatment was dexamethasone treatment if I understood correctly. Based on what I have said thus far, do you believe the same treatment plan that I had last FET plus the use of dexamethasone through 10 weeks gestation would give us a positive pregnancy. What about the use of IVIg? I have read that it can be very costly and the intralipid infusion can be just as effective but may need to be done multiple times to lower one’s NK cell count. I am desperate for answers and am interested in hearing anything you might have to say about my case.

Thank you in advance for your time,

Nichole Hallock

reply
Dr. Geoffrey Sher

When confronted with “unexplained” IVF failures where morphologically good embryos were transferred, the question arises as to whether the problem is due to inherent egg/embryo “incompetence” (which usually equates with an irregular chromosomal configuration [aneuploidy]) or whether it is due to an implantation dysfunction. The younger the woman and the higher the quality of available embryos (preferably blastocysts), the less likely it is that the fault lies with embryo “incompetence” and the greater is the likelihood that it is due to underlying implantation dysfunction.
The most common causes of implantation dysfunction are:
a) A “thin uterine lining”
b) A uterus with surface lesions in the cavity (polyps, fibroids, scar tissue)
c) Immunologic implantation dysfunction (IID)
Implantation dysfunction (anatomical or immunologic) is a common cause of repeated “unexplained” IVF failure with good embryos. This is especially the case in young ovulating women who have normal ovarian reserve and have fertile partners. Failure to identify, typify, and address such issues is, in my opinion, an unfortunate and relatively common cause of repeated IVF failure in such women.

HELPFUL ADDITIONAL INPUT:
I urge you to access my new blog on this website. When you get to the “home page” of the Blog, find the “search bar” and type in any of the articles below by title, “click” and you will immediately be taken to these. While on this blog, please take the opportunity to post any questions or comments with the full expectation that I will (as always) respond promptly.

• Controlled Ovarian Stimulation (COS) for IVF: Selecting the ideal protocol
• Ovarian Stimulation for IVF using GnRH Antagonists: Comparing the Agonist/Antagonist Conversion Protocol.(A/ACP) With the“Conventional” Antagonist Aproach
• Ovarian Stimulation For Women with Diminished Ovarian Reserve (DOR) and in Older Women undergoing IVF
• Ovarian Stimulation for IVF: Comparing “conventional” use of GnRH antagonists to the Agonist/Antagonist Conversion Protocol (A/ACP)
• IVF: Factors Affecting Egg/Embryo “competency” during Controlled Ovarian Stimulation(COS)
• The BCP: Does Launching a Cycle of Controlled Ovarian Stimulation (COS). Coming off the BCP Compromise Response?
• Diagnosing and Treating Infertility due to Diminished Ovarian Reserve (DOR)
• IVF Failure and Implantation Dysfunction: The Role of Endometrial Thickness, Uterine Pathology and Immunologic Factors
• Unexplained IVF Failure
• 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)
• Traveling for IVF from Out of State/Country–
• A personalized, stepwise approach to IVF at SIRM”; Parts 1 & 2 (posted March, 2012)
• The Role of Nutritional Supplements in Preparing for IVF
• Frozen Embryo Transfer (FET): What Does it Involve?
• Hereditary Clotting Defects (Thrombophilia)
• Male Factor Infertility
• The Sperm Chromatin Structure Assay (SCSA): A Measure of the Potential of Sperm to Help Propagate a Viable Pregnancy..

I invite you to call 702-699-7437 or 800-780-7437 and set up a one hour Skype consultation with me to discuss your case in detail.

I also suggest that you access the 4th edition of my book ,”In Vitro Fertilization, the ART of Making Babies”. It is available as a down-load through http://www.Amazon.com or from most bookstores and public libraries.

Geoff Sher

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plex

Hi Dr. Sher,

Lovely blog.
At what stage would you recommend an immunological test to your female patients?
Also, are you familiar if this is something commonly practiced in Europe?

Thank you

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Dr. Geoffrey Sher

Immune testing is unfortunately not often pursued, in my opinion to the detriment of many patients. Also, when it is recommended, the wrong tests are often ordered and the testing not reliable. There are few Reproductive Immunology Reference Laboratories that can do these tests adequately…and to my knowledge, none are in Europe.

IMPORTANT INFORMATION:
I suggest that you access my Blog on this website, find the “search bar”. Type in selected topics that you wish to review (as below), “click” and you will immediately be taken directly to the selected article(s).

• IVF Failure and Implantation Dysfunction: The Role of Endometrial Thickness, Uterine Pathology and Immunologic Factors
• Unexplained IVF Failure
• 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)
• Traveling for IVF from Out of State/Country–
• A personalized, stepwise approach to IVF at SIRM”; Parts 1 & 2 (posted March, 2012)
• The Role of Nutritional Supplements in Preparing for IVF
• Frozen Embryo Transfer (FET): What Does it Involve?

I invite you to call 702-699-7437 and set up a one hour Skype consultation with me to discuss your case in detail.

I also suggest that you access the 4th edition of my book ,”In Vitro Fertilization, the ART of Making Babies”. It is available as a down-load through http://www.Amazon.com or from most bookstores and public libraries.

Geoff Sher

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