Immune modulation with IVIG

Every day, our immune system is in a delicate balance between attack and calm. Always poised and ready to attack an invading organism, but not so active that it damages our own bodies. However, in women with immune-mediated infertility, their immune system is not properly balanced and can not be down-regulated in the presence of an embryo. The goal of a reproductive immunologist is to push the immune system slightly in the direction of an embryo-accepting immune system without over-suppressing the immune system. This must be done BEFORE fertilization occurs and during pregnancy. A very good and detailed reproductive immunologist will order numerous tests to predict how the patient’s immune system will respond to an embryo and to various treatments. Once this knowledge is obtained, a detailed treatment plan will be created and may include a number of medications such as Prednisone, IVIG, Neupogen, Humira, as examples. Many times, a combination of these medications is necessary to address different aspects of our very complex immune system. Some medications work better than others for different situations or a proper combination of more than one medication may be necessary.

Today’s blog is about Intravenous Immunoglobulin (IVIG). IVIG can be an important part of a successful infertility treatment protocol.  IVIG is an immune modulating treatment that tips the mother’s immune system in favor of the embryo. IVIG can non-specifically shield the embryo from the mother’s immune system, it can suppress immune reactions against the embryo, it can decrease the production of antibodies that may cause immune destruction of the embryo, it can increase proper placenta formation by increasing growth factors such as G-CSF, and it can increase the number and activity of T regulatory cells that can suppress immune attack of the embryo. When properly administered, IVIG can help a mother’s dreams come true.

IVIG is not a one size fits all medication. There have been some studies that do not show an advantage to using IVIG over a placebo control. Most of these studies are done on a randomly selected population of women who either have implantation failure or multiple miscarriages. Testing has not been done on these women to show that they need immune treatments to have a baby. The research subjects are then given a standard dose of IVIG or a placebo control either before ovulation or upon a positive pregnancy test. Often the dose of IVIG that is prescribed is low and is not even equivalent to the dosing that is used in other instances where the immune system needs to be calmed, such as in autoimmune disease. The randomly selected research subjects are given IVIG at equally spaced times during pregnancy. NO testing is done prior to or during pregnancy to see how much IVIG is needed (if it is needed at all) and how often the IVIG must be administered before ovulation and during pregnancy. Since proper testing and treatment is not done, the results are often inconclusive. In order for immune treatments to work, a treatment protocol must be individually tailored to each patient’s immune system. If testing is done both before and during pregnancy to determine the appropriate immune modulating treatment protocol, a healthy pregnancy will more than likely be achieved. IVIG played an important role in both of my pregnancies and I have 2 healthy children because of it!

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Eating Vitamin D – A Recipe…

Eating a healthy and vibrant diet is very important for preserving and enhancing fertility. Although it takes time and may seem overwhelming at first, adhering to a Paleo or even an autoimmune Paleo diet can be very good for fertility and general health, especially for women and men with autoimmune disease or with immune mediated infertility.

This recipe, Salmon in Lemon Brodetto with Pea Puree, is adapted from Giada Delaurentiis’ cookbook called “Giada’s Kitchen” – http://www.giadadelaurentiis.com/books/. I am posting it today to go along with my last blog post about vitamin D. Salmon is a GREAT natural source of vitamin D. This recipe also contains healthy omega 3 fatty acids (from the salmon), vitamin C (from the lemon brodetto), and B vitamins (from the pea puree). Although peas are not allowed on a strict Paleo diet, I still like to eat peas because of their high nutrient content and vibrant color. If you would like to omit the pea puree, serve the salmon with the lemon brodetto and a side of roasted asparagus for a delicious and nutritious meal. I choose all organic produce and ingredients and ALWAYS use wild caught salmon. Please, never, ever buy or eat farmed salmon.

Salmon recipe

Ingredients for 4 servings

Lemon Brodetto

2 tablespoons extra virgin olive oil

1 shallot, diced

2 lemons, one zested and both juiced

2 cups low sodium, gluten free, organic free range chicken broth (I like Trader Joe’s brand)

1 tablespoon chopped fresh mint

Pea Puree

2 cups frozen, organic peas, thawed (around 10 oz)

1/4 cup fresh mint leaves

1/2 teaspoon kosher salt

1/2 teaspoon freshly ground pepper

1/4 cup olive oil (the original recipe calls for 1/2 cup, I prefer to use less olive oil in my recipe)

1/4 cup parmesan cheese (please omit if adhering to a Paleo diet)

Salmon

4 (4- to 6- ounce) wild boneless salmon fillet

Salt and pepper

Directions

To make the lemon brodetto. Warm the olive oil in a medium sauce pan over medium heat. Add the shallots and sauté until tender about seven minutes. Add the lemon zest, lemon juice, and the broth. Bring to a simmer, cover, and keep warm over low heat.

To make the pea purée. Combine the peas, mint, garlic, salt, and pepper and a food processor and purée. With the machine running, add the extra virgin olive oil in a steady drizzle. Transfer the pea purée to a small bowl and stir in the Parmesan cheese (the parmesan can be omitted if you are eating a Paleo diet). I have decreased the amount of Parmesan to 1/4 cup from the original recipe that calls for 1/2 cup. Set aside.

To make the salmon. Preheat oven to 450°F. Lightly grease a glass baking dish with olive oil. Baked salmon for 8 to 10 minutes or until cooked as desired. If desired, the salmon can be cooked on the stove top in a few tablespoons of olive oil (this is how it is cooked in the original recipe. I prefer cooking in the oven because the fish comes out less greasy tasting).

To assemble the dish. Stir one tablespoon of chopped mint into the lemon brodetto and divide among four shallow soup bowl. Place a large spoonful of pea purée into the center of each. Place a salmon piece on top of each mound of pea purée and serve immediately. Garnish with lemon zest and chopped mint. Enjoy!

Sunshine and Supplements

It’s a cold and cloudy day in Southern California, a perfect day to drink a hot cup of green tea and write. I haven’t written a blog post in over a year, so a million ideas are floating though my head – from inflammation, endometriosis, and HLAs to kefir, yoga and gluten. Where to start? There is so much to share. So I decided to start with an easy one….vitamin D. Why is vitamin D easy? Because many women and men are vitamin D deficient and vitamin D plays a crucial role in our health and fertility. Testing for vitamin D deficiency and increasing vitamin D intake is quick, easy and can make a big difference. So it’s a no brainer!

Deficiency in vitamin D has a significant impact on health and fertility. Studies have shown that couples that have propeSienna and Chiaria sunshine vitamin D blogr vitamin D levels have a 4 times higher chance for a successful IVF cycle. Vitamin D is thought to play a role in both female in male fertility in the following ways:

Polycystic ovary disease – vitamin D supplementation has been shown to improve AMH levels, decrease inflammation, and improve insulin, blood pressure and lipid levels. This leads to better ovarian function and pregnancy rates.

Endometriosis – vitamin D can inhibit the survival of endometrial tissue in the peritoneal cavity and restrict disease development. Vitamin D is also anti-inflammatory and can lower inflammatory cytokines that are associated with endometriosis.

Premature ovarian failure – vitamin D can increase fertility by modulating androgen activity and can have a positive effect on AMH level and follicle development.

Blood sugar regulation – vitamin D can help with insulin resistance and help to regulate blood sugar. This leads to lower fasting insulin levels and improved ovarian function and health since insulin is inflammatory.

Anti-inflammatory – vitamin D inhibits the production of the pro-inflammatory cytokine TH17. Vitamin D can also increase CD4+CD25+ T regulatory cells that play a calming role in the immune system and help the immune system accept the developing embryo. T regulatory cells can also produce IL10 which improves uterine blood flow and down regulates the immune response toward an embryo. Vitamin D also acts on dendritic cells that play an important role in maintaining immune tolerance during pregnancy.

Sperm – maintaining vitamin D levels within the normal range is important for proper sperm development and function. Low vitamin D is associated with low sperm number and motility while high vitamin D is associated with defects in sperm morphology.

The optimal blood serum concentration of Vitamin D is between 50 and 125 nmol/L. Your doctor can easily order this test or you can order it yourself at a lab such as Direct Labs. Vitamin D is also known as vitamin D – 25 hydroxy, 25OH vitamin D, 25-hydroxy vitamin D. We can obtain vitamin D in three ways. 1) from sunlight with no sunscreen. This is not effective for people that live the Northern United States between the months of October and May. 2) from food sources such as fatty fish (salmon, tuna, sardines), eggs, shitake mushrooms, and fortified cow’s milk and cereal. 3) from supplementation with vitamin D3. Most of my clients take 1000-3000IU of vitamin D3 daily to get their levels within the normal range.  Please ask your doctor to test your levels and help you to determine how much vitamin D you may need.

Recommendation…..

I never get tired of receiving photos and letters from my clients after they have their babies. Here is one that I received this week:

After five miscarriages in four years and a dozen failed fertility treatments, I was beginning to think my dream of having another child would never materialize.  Fortunately, a friend referred me to Karen.  Even before I decided to work with Karen, she had a lengthy consultation with me over the phone.  She confidently assured me that she would find a cause and solution to my secondary infertility and recurrent miscarriages.  After evaluating my lab work, she sent me a comprehensive evaluation of my immunologic and thrombotic profile.  She suggested a treatment plan, and within a few months I was pregnant with a baby I was able to carry to term.  As a physician myself, I was very impressed with Karen’s knowledge and expertise.  I can’t thank Karen enough and recommend her services to anyone struggling with infertility.

Resolve to know more…about Reproductive Immunology

Resolve to know more……about Reproductive Immunology. If you are struggling with unexplained infertility or recurrent miscarriage take 10 minutes today to learn more about the field of Reproductive Immunology. I know this field is controversial, but it is full of women who have had success after multiple IVF failures or miscarriages. The best way to learn more about Reproductive Immunology is to find women who have had success and speak to them. Join a Reproductive Immunology support board or just simply Google Reproductive Immunology. I promise we are out there! There are also many specialists (like me) who are devoted to this field and can help you determine if your immune system is interfering with your ability to have a baby. And to all of my fellow infertility survivors who were successful after treating their immune system, please resolve to take 10 minutes today to share your story. In order for people to “know more” , we need to “share more”.

Don’t ignore…

Don’t ignore your inner voice and intuition. These played a very powerful role in my own infertility journey and I am thankful every day that I listened to my own voice and not my diagnosis of unexplained infertility. My intuition was telling me that there was a piece of the puzzle missing and that I would continue to look for it until I had a baby or until my inner voice was quiet and my questions had been answered.

Ten years ago, I was stuck in the world of infertility. I was seeing reputable Reproductive Endocrinologists and doing everything that I was supposed to do. Month after month, procedure after procedure resulted in a negative pregnancy test. At almost every appointment, I would bring up my immune system as a cause for my infertility and at every appointment my doctors would shake their heads and say, no, that could not be it, it must be your eggs. Yet, the little voice inside my head got louder and I began to do some research. Since the immune system played such a vital role in allowing an embryo to implant and survive, why couldn’t something go wrong with this process? Why couldn’t my immune system be destroying my embryos before they could properly implant and give me a positive pregnancy test. It seemed to make sense to me, by that point I had studied Immunology for years and even had a Ph.D. in Immunology under my belt. So as I failed 9 IUIs and  3 IVFs, my inner voice continued to ask the question, What About My Immune System?

Finally, I decided that it was time to listen. I quit infertility treatments and found an amazing doctor that actually agreed with me! And viola – yes, viola – I was pregnant. It was amazing! I used Prednisone, IVIG, baby aspirin, Folgard and Lovenox and I got pregnant naturally right away! For my second daughter I needed to add in a few more treatments (LIT and Metformin) and conceiving her was just as easy. Today I have a 6 year old and a 3 years old and I am thankful everyday for them and for listening to my inner voice.

The journey of infertility changes us all. In the end, I feel that I was changed for the better. I am an appreciative mom of two beautiful and talented daughters and I have one of the most rewarding careers anyone could ask for. I help women listen to their own inner voice  and intuition. I ride the infertility roller coaster with them. I help them find the solutions to their infertility or miscarriages and I get to celebrate with them when their babies are born! In closing, I would like to share an inspiring quote  “Don’t be trapped by dogma — which is living with the results of other people’s thinking. Don’t let the noise of others’ opinions drown out your own inner voice. And most important, have the courage to follow your heart and intuition.” (Steven Jobs).

This post was written as part of National Infertility Awareness Week and Resolve.org’s “Don’t ignore” campaign.

Anti-inflammatory diet

Last week, I read about a study involving 147 infertility patients at Massachusetts General Hospital Fertility Center. The study found that monounsaturated fat, like that found in olive oil, sunflower oil, nuts, seeds, and avocados was better for would be mothers than other types of dietary fat. Women who ate the highest proportion of monounsaturated fat in their diet were 3.4 times more likely to have a baby after IVF. While women that ate mostly saturated fat, such as that found in butter and red meat, produced fewer eggs and had a lower birth rate. What I found most interesting (but not surprising) about this study was that the researchers suggested that monounsaturated fats could improve fertility by lowering INFLAMMATION and affecting INSULIN sensitivity. As you all know, I believe that many women are failing their fertility treatments or having miscarriages because their immune system. Chronic inflammation can drive the immune system to be over active against a pregnancy and not allow the embryo to implant or survive. It can also decrease blood flow to the uterus and damage eggs. Does this mean that all of my clients are going to stop their IVIG or Prednisone and just start eating avocados? Probably not. It does mean that decreasing chronic inflammation can help all women achieve a healthier pregnancy. So if you are just starting out and want to make a few changes that you can do at home, consider trying an anti-inflammatory diet. If you have celiac, definitely avoid gluten. And if you have PCOS, the more that you can do to avoid sugar and simple carbohydrates in order to maintain a stable insulin level and decrease inflammation the better. And in the meantime…..have your immune system tested. The top tests that I like to see are NK cytotoxicity (including CD56), Th1/Th2 cytokine ratios, Leukocyte antibody detection panel, HLA, and T regulatory cells, to name a few.