Reproductive Immunology For Miscarriage Prevention And Endometriosis

REPRODUCTIVE IMMUNOLOGY FOR MISCARRIAGE PREVENTION AND ENDOMETRIOSIS

RFC is very honored because it was chosen by BRI Reproductive Immunology and Endometriosis Surgical Center to continue their legacy after they closed on 08/20/2024, since Dr. Merhi has an extensive expertise in the field of Reproductive Immunology.That is why we created RFC Reproductive Immunology Program (email us at RFCimmune@RejuvenatingFertility.com)

What Is REproductive Immunology?

It is a field of medicine that evaluates the interactions between the immune system and components related to the reproductive system such as maternal immune tolerance towards the embryo or fetus. We use reproductive immunology testing to try to find explanation for unexplained reasons of infertility, recurrent miscarriages, and pregnancy complications observed when this state of immunological tolerance is not successfully achieved.

The immunological system of the mother plays an important role in pregnancy because the mother’s body considers the embryo (which is half sperm and half egg) is “half foreign” and thus it needs to make sure that the embryo will not be rejected.

During pregnancy, immunological events that take place within the body of the mother are crucial in determining the healthiness of both the mother and the fetus. In order to provide protection and immunity for both the mother and her fetus without developing “rejection reactions,” the mother must develop “immune tolerance” to her embryo/fetus.

The placenta also plays an important part in protecting the embryo from the mother’s immune system attack. Secretory molecules produced by placenta and maternal uterine immune cells work together to develop a functioning placenta.

This field of Reproductive Immunology is known to help in the treatment of endometriosis, inflammation-related infertility, and previously failed in vitro fertilization
(IVF) treatments.

For example, Endometriosis could be associated with other immune and inflammatory disorders, such as:

  • Thyroid disorder
  • Rheumatoid arthritis
  • Systemic lupus erythematosus (SLE)
  • Fibromyalgia
  • Celiac disease
  • Multiple sclerosis
  • Inflammatory bowel disease

Uterine Natural Killer (NK) cells

The maternal immune system, specifically within the uterus, undergoes changes in order to allow for implantation and protect a pregnancy from “body attack.” One of these changes are alterations in the uterine Natural Killer (NK) cells. NK cells are part of our normal immune system and are responsible for attacking infections. However, the number of NK cells are different during a healthy pregnancy. In the first trimester of pregnancy, NK cells are among the most abundant immune cells present, but the number of NK cells present slowly declines up until delivery of the baby.

woman-suffering-from-infertility-1

An increase in the numbers of NK cells in the uterus has been associated with several human reproductive disorders, including recurrent implantation failure, recurrent miscarriages, and infertility. 

What is endometriosis and how is it diagnosed?

Up to 50% of infertile women have endometriosis. Endometriosis occurs when tissue of the uterine lining grows outside of the uterus and goes on other organs in the abdomen such as fallopian tubes, ovaries, bowel and even bladder. It can affect the reproductive system at all levels; i.e, the ovaries, the uterus, and the fallopian tubes. Endometriosis is under diagnosed and commonly undertreated because the only diagnosis is by undergoing a major surgery. This delay in diagnosis can contribute to poor fertility outcome.

The diagnosis of endometriosis is suspected based on the patient’s history and her symptoms. It is confirmed after a physical examination and imaging techniques such as ultrasound and MRI. However, surgery is the gold standard for its diagnosis.

Endometriosis should be considered in situations where multiple IUI, IVF, embryo transfer, or even egg donor cycles had failed. Endometriosis, which is an inflammatory process associated with immune system dysfunction, must be considered as one of the possible contributing factors. 

Endometriosis is associated and could be a symptom of other immune and inflammatory disorders such as thyroid disorder, rheumatoid arthritis, systemic lupus erythematosus (SLE), fibromyalgia, celiac disease, multiple sclerosis, and inflammatory bowel disease.

It is well known that women with endometriosis have poorer outcome in IVF because they tend to have lower ovarian reserve, poorer egg and embryo qualities, and lower implantation rates.

MISSION OF RFC’s REPRODUCTIVE IMMUNOLOGY
PROGRAM

Our goal is to provide a simple and stress-free service, optimizing the chances for a successful journey to parenthood.

After extensive research and training in the field, RFC became one of the leaders in the field of Reproductive Immunology which is committed to helping couples who have experienced recurrent implantation failure, recurrent pregnancy losses, or pregnancy with a history of or active autoimmune disease in order to achieve a successful pregnancy. We will perform comprehensive analysis that will help generate your unique immunological treatment plan to allow us to effectively manage your IVF cycle and your early pregnancy.

We are committed to helping women who have

  1. miscarriages
  2. endometriosis
  3. failed IVF
  4. implantation failure
  5. had a pregnancy with a history of active autoimmune disease (Hashimoto’s disease and others).

SUCH WORK-UP AND TREATMENTS INCLUDE:

  • Intra-lipids infusions to lower NK (Natural Killer) cells
  • NEUPOGEN (G-CSF)
  • Endometrial biopsy for lining inflammation and receptivity
  • Intravenous immunoglobulins (IVIG)
  • Omega 3 supplementation such as EPA and DHA
  • Steroid to lower inflammation such as Prednisone
  • Blood thinners such as Lovenox, Heparin, or baby aspirin
  • Other treatments based on each patient medical history such as Plaquenil

INTRALIPIDS INFUSION:

What are they?

Intralipids are a synthetic fat emulsion and are usually made from 1.2% egg yolk phospholipids, 10% soybean oil, 2.25% glycerin and water.

How do they work?

Intralipids deactivate natural killer cells in a woman’s body which may prevent embryos from implanting and growing properly in the uterus.

Who might benefit?

  • If you suffer from Recurrent Pregnancy Loss
  • If you suffer from Recurrent Implantation Failure
  • If you have elevated NK cells

When to receive the infusions?

  • 1-2 weeks before the embryo transfer
  • Another infusion on the day of or before the embryo transfer
  • Then every 2 weeks until 9-12 weeks of pregnancy to keep the NK cells deactivated until the pregnancy can override the signals being sent by my immune system.
  • Each infusion takes approximately 45 minutes.

Summary Statement by the ASRM

  • There is insufficient evidence to routinely recommend intravenous fat emulsions for infertile women pursuing IVF.
  • Additional studies are needed to identify populations where benefits may exist but are not proven.

PRP (PLATELET-RICH PLASMA) INFUSION IN THE UTERUS

Platelet rich plasma (PRP) therapy takes your own blood, concentrates its healing properties contained in the plasma and then reinjects it back into you to speed healing. Administration of the patient’s own PRP into the uterine cavity is beneficial for endometrial thickness and has been shown to improve the rates of implantation and clinical pregnancy achieved in IVF.

In the human body, platelets are about 10 percent of the blood’s cellular components. In PRP, your blood platelet concentration is increased to 90 percent, greatly increasing your blood’s healing power. PRP can be up to 10 times richer in the concentration of healing growth factors than normal blood, which helps speed the healing process. Because the treatment uses your own blood, PRP is safe with minimal risk of any adverse reaction.

PRP infusion in the uterine lining is done like an IUI or like a saline ultrasound. It can help with better implantation by:

  1. Increasing lining thickness
  2. Increasing stickiness of the lining

MEDICAL REFERENCE(S):

  1. Zaher Merhi et al. Ozone Sauna Therapy (OST) and Pulsed Electromagnetic Field Therapy (PEMF) delivered via the HOCATT machine could improve endometriosis pain along with lowering serum inflammatory markers. Am J Reprod Immunol. 2023;89:e13690.
  2. Zaher Merhi et al. Mechanisms of premature ovarian failure: reappraisal and overview. J Reprod Med. 2007 Jul;52(7):623-9.
  3. Zaher Merhi et al. Effect of weight loss by bariatric surgery on the risk of miscarriage. Gynecol Obstet Invest. 2007;64(4):224-7.
  4. Zaher Merhi et al. Recurrent pregnancy loss and obstetric outcome. Merhi Z et al. Int J Gynaecol Obstet. 2007 Jan;96(1):28-9.
  5. Zaher Merhi et al. A case of 46,X,der(X)t(X;X)(q22.1;p11) Xq22.1–>Xqter in a 12-year-old girl with premature ovarian failure. Gynecol Obstet Invest. 2007;63(3):137-9.
  6. Zaher Merhi et al. Effect of bariatric surgery on peripheral blood lymphocyte subsets in women.  Surg Obes Relat Dis. 2009 Mar-Apr;5(2):165-71.
  7. Zaher Merhi et al. Mannose binding lectin genotypes are not associated with increased risk of unexplained recurrent pregnancy loss. J Assist Reprod Genet. 2013 Jun;30(5):723-7.
  8. Zaher Merhi et al. Role of pro-inflammatory advanced glycation end-products in obesity-related ovarian dysfunction.  Minerva Endocrinol. 2014 Sep;39(3):167-74.
  9. Zaher Merhi et al. Adiposity Alters Genes Important in Inflammation and Cell Cycle Division in Human Cumulus Granulosa Cell. Reprod Sci. 2015 Oct;22(10):1220-8.
  10. Zaher Merhi et al. Proinflammatory Monocyte Chemotactic Protein-1 (MCP-1) plays a role in ovarian dysfunction related to high-fat diet-induced obesity. Syst Biol Reprod Med. 2020 Aug;66(4):236-243
  11. Zaher Merhi et al. Pro-inflammatory advanced glycation end products: A link between metabolic and endothelial dysfunction in polycystic ovary syndrome?  Metabolism. 2015 Nov;64(11):1564-73.
  12. Zaher Merhi et al. Dietary Pro-inflammatory Advanced Glycation End Products (AGEs) could alter ovarian function in mice.  Mol Cell Endocrinol. 2020 Jun 15;510:110826
  13. Zaher Merhi et al. Ovarian kisspeptin expression is related to age and to monocyte chemoattractant protein-1 (MCP-1).  J Assist Reprod Genet. 2016 Apr;33(4):535-43
  14. Zaher Merhi et al. Serum and follicular fluid monocyte chemotactic protein-1 levels are elevated in obese women and are associated with poorer clinical pregnancy rate after in vitro fertilization: a pilot study.  Fertil Steril. 2017 Mar;107(3):632-640.
  15. Zaher Merhi et al. Follicular fluid [of the anti-inflammatory] soluble receptor for advanced glycation end-products (sRAGE): a potential indicator of ovarian reserve. J Clin Endocrinol Metab. 2014 Feb;99(2):E226-33.
  16. Zaher Merhi et al. Vitamin D increases serum levels of the anti-inflammatory soluble receptor for advanced glycation end products in women with PCOS. J Clin Endocrinol Metab. 2014 May;99(5):E886-90.
  17. Zaher Merhi et al. Impact of Dietary Advanced Glycation End Products on Female Reproduction: Review of Potential Mechanistic Pathways.  Nutrients. 2022 Feb 24;14(5):966