More on Reproductive Immunology
Reproductive immunology is concerned with the way a woman’s immune system reacts if she becomes pregnant. Usually, your immune system works by fighting off any invading cells that it doesn’t recognize because they don’t share your genetic code. Some scientists have suggested that the same thing may happen to a fetus because it has a different genetic code from its mother’s. A woman’s body may ‘reject’ the fetus because her immune response is not being properly suppressed.
This theory has been widely discredited and there is no convincing evidence that immune rejection of the fetus ever happens in women with fertility problems. Instead, scientists now know that during pregnancy, the mother’s immune system works with the immune system of the fetus to help the placenta develop.
The information below is based on the latest research and expert views about reproductive immunology (to February 2015).
The term autoimmune disease refers to a varied group of more than 80 serious, chronic illnesses that involve almost every human organ system. In all of these diseases, the body’s immune system becomes misdirected, and attacks the very organs it was designed to protect. About 75% of autoimmune diseases occur in women, most frequently during the childbearing years.
“Affected women need two layers of treatment: a first layer to conceive, and a second to prevent pregnancy loss after conception.”
Autoimmune diseases can affect connective tissue, the tissue that binds together various tissues and organs. It can also affect the nerves, muscles, endocrine system, and gastrointestinal system. There are a large number of autoimmune diseases, with multiple sclerosis, Hashimoto’s thyroiditis, rheumatoid arthritis being some of the most common.
Because an abnormal immune function can affect fertility as well as miscarriage risk, affected women need two layers of treatment: a first layer to conceive, and a second to prevent pregnancy loss after conception. This is a very important point: it would not make sense to receive fertility treatment to get pregnant, only to experience an emotionally painful and potentially preventable pregnancy loss.
More on NK Activated Cells
Suffering a miscarriage can be a very distressing experience but for many women, their next pregnancy is a normal one. For women, however, who suffer a recurrent miscarriage, where they have three or more in a row, it can be utterly devastating.
More frustrating still is that in many cases – more than half – doctors are unable to find an underlying cause or offer more than just a handful of options for treatment.
Now researchers from Warwick University claim to have made a breakthrough. Not only by making a firmer case for the role of natural killer (NK) immune cells in some cases of recurrent miscarriage, but also in bridging the gap between scientists and the medical profession in what has become a controversial area of research.
Despite their name, NK cells actually play a beneficial role in the development of an embryo. But abnormally high levels of NK cells are found in the uterus of some women (around a sixth) who recurrently miscarry. NK cells are a key player in the innate immune system, which can be triggered to defend the body from infection. One theory is that in some cases they may stop an embryo implanting in the womb.
However, little is known about this mechanism. And the potential role that NK cells might play in recurrent miscarriage has caused significant controversy.
The authors of the new study, published in The Journal of Clinical Endocrinology & Metabolism, make a link between more NK cells in the lining of the womb and a deficient production of natural steroids. Having this deficiency, in turn, leads to a reduction in the formation of fats and vitamins that provide essential nutrition during pregnancy. They suggest that NK cells can be used as an indicator of steroid deficiency.
Steroids, which are thought to work by reducing the percentage of NK cells in the womb, are commonly used as a treatment for recurrent miscarriage and do appear to help some women to go on to have a normal pregnancy. But many experts agree this is based more on empirical evidence that a firm scientific understanding.
Siobhan Quenby, Professor of Obstetrics at Warwick Medical School and one of the authors of the study, said treatments for recurrent miscarriage often came “out of guesswork, not science” and said the research provided an “excellent scientific justification for steroid-based treatment to prevent miscarriage.”
“If you have NK cells in the blood they do things like fight infection. In the uterus they also have a good function – for example, they help in the development of the blood supply to the fetus.
“But we now have some light at the end of the tunnel; in some ways everyone is right. NK cells are good but high-end NK cells are also associated with local steroid deficiency.” Quenby said that the research suggests the deficiency causes an increase in the higher percentage of NK cells, rather than the other way round.
Nick Macklon, Professor of Obstetrics and Gynaecology at Southampton University and an expert in IVF, said: “The problem is that we haven’t really understood the mechanisms behind recurrent miscarriage. We now know that an important determinant is the lining of the womb and how it helps embryos to implant. A lot of treatment has been empirical, adopting theoretical treatments, not on the science.
“Quenby has done a lot of work to try and understand the role of NK cells, which hasn’t been very clear. The key thing is that the researchers aren’t saying they are bad but when there’s an increase it might be a useful marker. It could allow for treatment to be rationalized. Steroids have side effects and have been used very blindly. But they do seem to make a difference and also to the needs of doctors and patients looking for help.”
Macklon said recurrent miscarriage was probably caused by a number of different factors across different cases. “One possible cause is the ability of the lining of the womb to recognize and select good embryos and in some women, it isn’t able to do this early enough.”
A previous small randomized trial carried out by Quenby showed a marked difference in the chances of going on to have a baby in a group of 20 women treated with steroids versus an identically sized group given placebos. But she admits that to draw solid conclusions, a trial size of around 700 women is needed.
Request an Appointment
FAQs
Hysteroscopy is the inspection of the uterine cavity that allows for the diagnosis and treatment of various uterine conditions. Some of which, could lead to fertility problems.
Uterine Septum (Septate uterus)
This is the most common uterine malformation and a common cause of miscarriage. It is unclear whether a uterine septum increases the chances for infertility or not. A wedge of tissue is present inside the uterine cavity, which divides it into two halves (also called uterine horns).
When seen through a hysteroscope, the uterine horns are seen as two dark openings separated by a wedge of tissue. By introducing an electrode through the hysteroscope, the septum can be shaved or vaporized all the way to the top of the cavity. The finished product is a uterine cavity that is unified into one large space instead of divided in two.
Polyps
These are uterine growths a few millimeters to centimeters in size. Polyps arise from the uterine lining (endometrium). A polyp may be attached to the uterine wall directly or by a thin “stalk”.
Patients often have no symptoms from polyps but will occasionally notice irregular vaginal bleeding. This bleeding may occur in between periods or cause the period to be longer in duration or heavier than normal.
Polyps are also associated with an increased risk for miscarriage. Large polyps, which occupy the majority of the uterine cavity, are also probably responsible for infertility. Small polyps can be most easily vaporized in place. Polyps which are attached by a stalk can sometimes be removed by cutting through the stalk and removing the entire polyp through the cervix. Larger polyps may have to be removed by shaving small strips one at a time until the polyp is completely gone, or slightly deeper, taking a margin of the myometrium. This tissue is sent out for pathology.
Fibroids
These benign tumors arise from the muscle layers of the uterus. Often they will stay in the muscle layer but on occasion, fibroids can grow into the uterine cavity. Like polyps, fibroids can cause bleeding, infertility, and as well as miscarriage. Removal of fibroids from the uterine cavity is performed using the same methods as for polyps.
Scar tissue
Scar tissue inside the uterine cavity, also called adhesions, can arise from infection or trauma to the uterine lining. Although rare, the most common cause for uterine adhesions to form is from a previous D&C procedure. Scar tissue inside the uterus can be small and isolated to a certain spot. This type of adhesion looks like a band running from one wall of the uterus to another. Sometimes adhesions take the form of two walls that are stuck together causing the cavity at that spot to be completely obliterated. In rare instances, the entire cavity can be obliterated. Uterine adhesions can cause infertility or miscarriage. If the uterine cavity is partially or completely obliterated, a woman may notice that her period are lighter or even stop altogether. Band adhesions can be easily cut restoring the normal anatomy of the uterine cavity. When the walls are stuck together, the surgeon must carefully dissect between them in order to separate the walls. This can be a very difficult process if there is little normal uterine cavity that remains to serve as a guide.
You will be able to watch the sonohysterogram on a monitor while it is being performed. Afterwards, the doctor will review the findings with you and answer any questions about those findings. If there are any abnormalities that are found on the inside of your uterus, don’t worry! Nearly all of these conditions are easily corrected with minimally invasive, outpatient surgery (usually with hysteroscopy).
Occasionally, a woman might experience some cramping during or after a hysterosonogram. If she desires, she may take 1-2 tablets of ibuprofen (Motrin or Advil) 1-2 hours before the procedure to decrease cramping. This may be repeated 3-4 hours later in the unlikely event that cramping persists.
The procedure for performing a sonohysterogram is very simple and usually takes about 5 minutes. In order to schedule a sonohysterogram, you will need to call with the first day of your period. You will be given an appointment for some time point after the bleeding from the period has ended but before it is thought that ovulation might occur. This ensures that the uterine lining is as thin as possible. This is important since it will assist the doctor in the visualization of the cavity. The hysterosonogram is performed in the office. Using a speculum, a very thin, soft, flexible plastic catheter will be inserted through the vagina and cervix into the lower part of the uterine cavity and a balloon is inflated. The speculum is then carefully removed so as not to disturb the catheter. A vaginal ultrasound probe is then placed into the vagina. Through the catheter, a small amount of saline (sterile salt water) is injected into the uterine cavity to separate the walls.
During a sonohysterogram, the ultrasound probe can be rotated to show the long axis of the uterus or a transverse axis. In the long axis, the uterine cavity appears long and ovoid. Sometimes after the procedure, a small amount of the saline fluid may leak out of the vagina. It is also possible that the patient may experience some bleeding or spotting. It is recommended that the patient wear a light pad or tampon for the rest of the day.
A hysterosonogram is often recommended for women who are having difficulty conceiving a pregnancy or for women who are having recurrent miscarriages. In some cases, a hysterosonogram may be used for a woman who is having abnormal vaginal bleeding. Since a sonohysterogram gives such a detailed view of the inside walls of the uterus, it can identify many abnormalities that might prevent a normal pregnancy from developing. Studies have shown that it can detect over 90% of abnormalities inside the uterus. Some of these abnormalities include:
- Polyps
- Fibroids
- Scar tissue
- Uterine septum
- Bicornuate Uterus
A sonohysterogram or SHG is a saline ultrasound, saline sonogram, or saline infusion sonogram. A sonohysterogram is a minimally invasive ultrasound procedure that can determine if there are abnormalities inside the uterus that might interfere with pregnancy. It is important to have an evaluation of the uterine cavity with a sonohysterogram or other method before proceeding with an IVF cycle. This test involves no radiation, and there are very few risks from the procedure. Compared to a regular ultrasound, a sonohysterogram is better at detecting abnormalities on the inside walls of the uterus because it involves infusing sterile fluid inside the uterus. This way, the walls of uterus separate from each other and any abnormalities that might have been hiding right along the sides of the walls will be easily identified.
Here is an example to help understand why we do a sonohysterogram. Think of your uterus like a collapsed balloon. If there was a small growth or bump on the inside wall of the collapsed balloon, it might be hard to see since the top and bottom walls are touching each other. However, if we inflated the balloon, the small growth will be easier to see since it will likely be able to hang away from the wall.
Traditionally, the “best” way to look for abnormalities inside the uterus was a test called a hysteroscopy, which involves an out-patient surgery using a type of endoscope to look inside the uterus. However, in recent years, the techniques for a sonohysterogram have become so advanced that it has usually replaced hysteroscopy as the first procedure to look for abnormalities in the uterus. Compared to a hysteroscopy, a sonohysterogram is less invasive, less expensive and nearly as effective at detecting abnormalities.
AMH or anti-mullerian hormone is a hormone produced by the viable follicles (which contain eggs) that remain in the ovary. It is an excellent indicator of ovarian reserve. Young women with large numbers of healthy eggs tend to have high AMH levels whereas older women or women with a low number of healthy eggs will have lower levels of AMH. New information is suggesting that very high levels of AMH may not simply indicate a plethora of antral follicles, but may indicate a follicular dysfunction.
AMH levels do not fluctuate very much throughout the cycle and are not impacted by the levels of other hormones such as estrogen or progesterone.
Abnormal AMH levels are usually determined by comparing a woman’s own AMH level with that of a large group of women her own age who do not have infertility. For example, an AMH of 1.4 would be considered very low for a fertile 18-year-old but would be considered average for a 36-year-old.
Fertility decreases with age. This decrease is most likely due to aging of the eggs and the chromosomes inside them. The risk of miscarriage and chromosomal abnormalities in babies also increase with age. The most successful method for achieving a pregnancy and taking home a baby at advanced female age is with the use of egg donation.
Testimonials
The staff and Dr. Couvaras were so kind and understanding. They called me by name as soon as I walked in. Dr. Couvaras was incredibly knowledgeable and knew from the first visit what was going on and after tests came back he was 100% right. He was informative, personable and took care of my health needs as a priority. I never felt left on the back burner. Innovative for sure because now I have 3 amazing children!
My husband and I are so thankful for Dr. Couvaras and staff. We were struggling to have a family and stumbled across the IVF Phoenix website. We are from Canada and the staff was fantastic to deal with and very accommodating to work with. We always had support no matter what time of the day. We now have the most perfect beautiful little boy to complete our family!!! So grateful and blessed!!!
Dr. Courvaras is the best there is in the infertility world!! Our first baby is here because of him and his team. Our baby is 17 and will be graduating from high school in less than a month!! We have never forgotten him and the gift he helped us have!!
This is hands down the BEST fertility clinic in all of Az. Dr. Couvaras and Rhoda are amazing!! Not only are they compassionate and helpful beyond expectations they really look at the whole body and systems and get to the root of the problem. If you are even thinking about fertility go see this place first!
From the moment we met Dr. Couvaras, My husband and I felt totally comfortable, secure, and well informed. Additionally, the nurses and staff at IVF Phoenix provided prompt, efficient care with both expertise and patience. Whether ordering prescriptions, educating me on how to properly administer medications or explaining options and probable outcomes of specific treatment protocols, Dr. Couvaras, and his team were simply remarkable. I never felt alone, and appreciated the close guidance they provided throughout our entire treatment. I couldn’t be happier with the results! My husband and I are now 12 weeks pregnant, and are absolutely thrilled! I would recommend Ivf Phoenix to anyone who is interested in finding the cause of their infertility. We love and appreciate everyone at Ivf Phoenix, they are a 2nd family to us. We still can’t thank them enough for making our dreams come true!
IVF Bundled Packages
(Self Pay)
IVF WITH FRESH EMBRYO TRANSFER
$5800
Includes:
Excludes:
IVF WITH FROZEN EMBRYO TRANSFER
$7250
Includes:
Excludes:
IVF WITH BIOPSY & FROZEN EMBRYO TRANSFER
$9500
Includes:
Excludes:
* Once you have completed your consultation with one of our providers, we would be happy to customized a multi-cycle package for you if you are considering embryo banking.
Services
Confused about the next steps to successfully conceive and carrying to live birth?
Partner Insurance
Please note that the following listed insurance companies are those that we currently partner with. Please call your insurance provider and check to see if your treatment or procedure will be covered.

IVF TM Phoenix is proud to be a Center of Excellence with Optum

Arizona Foundation (AZFMC)

Blue Cross Blue Shield

Aetna
Zelis

Humana

WebTPA

MultiPlan

Banner Aetna

Bright Health Care
GEHA
Gilsbar

Cigna

UHC All Savers

Medica & Mayo Medical Plan
Meritain
AmeriBen
Private Healthcare Systems
TRICARE
United Healthcare
UMR

Liberty Healthshare

Kindbody