IVIg Therapy for immune-related Infertility: How It Helps with Implantation & Recurrent Pregnancy Loss

Intravenous immunoglobulin therapy in IVF is a form of immunotherapy used in reproductive medicine to address immune-related factors that may contribute to infertility. IVIg therapy involves the intravenous infusion of pooled human immunoglobulin G (IgG) antibodies obtained from healthy blood donors. These antibodies help modulate the immune response and reduce the risk of immune-mediated pregnancy loss. It is widely used in reproductive immunology to help regulate immune responses in women with immune-related infertility, recurrent implantation failure (RIF), or recurrent pregnancy loss (RPL).

Conditions Addressed by IVIg Therapy

IVIg therapy is primarily used to address immune-related infertility associated with autoimmune disorders (APS). Autoimmune disorders, such as systemic lupus erythematosus (SLE), rheumatoid arthritis, and antiphospholipid antibody syndrome, can contribute to recurrent pregnancy loss and implantation failure.

Reproductive Medicine Specialists also use Intravenous immunoglobulin (IVIg) therapy in cases associated with specific immune factors such as, elevated circulating natural killer (NK) cells, embryotoxins, abnormal NK cell activity, or unexplained recurrent spontaneous abortions.

How IVIg-Intravenous immunoglobulin therapy helps in enhancing IVF success

  1. Suppresses Overactive Natural Killer (NK) Cells
    • NK cells play a role in immune defense, but excessive activity can lead to embryo rejection.
    • IVIg reduces NK cell cytotoxicity, preventing the immune system from attacking the embryo.
    • This helps promote successful implantation in women with elevated NK cell activity.
  2. Modulates Cytokine Balance
    • The immune system relies on cytokines (signaling proteins) to regulate inflammation.
    • In women with immune-related infertility, a pro-inflammatory cytokine dominance (e.g., high TNF-α, low IL-10) can interfere with implantation.
    • Intravenous immunoglobulin therapy shifts the balance towards an anti-inflammatory state, creating a more receptive uterine environment, improving pregnancy outcomes in IVF
  3. Regulates T-Cell Activity and Autoimmune Responses
    • Overactive T-helper cells (Th1) can lead to autoimmune attacks on embryos.
    • IVIg Therapy reduces Th1 responses while promoting T-regulatory (Treg) cells, which help maintain immune tolerance during pregnancy.
    • This is particularly beneficial for women with autoimmune disorders like lupus, Hashimoto’s thyroiditis, or antiphospholipid syndrome (APS).
  4. Neutralizes Autoantibodies
    • Women with antiphospholipid antibodies (APAs), anti-nuclear antibodies (ANAs), or anti-thyroid antibodies may experience pregnancy loss due to clotting issues or immune rejection of the embryo.
    • IVIg binds to and neutralizes these harmful autoantibodies, reducing the risk of miscarriage.
  5. Improves Endometrial Receptivity
    • By reducing inflammation and immune rejection, using Intravenous immunoglobulin therapy in IVF enhances blood flow and implantation conditions.
    • This is particularly helpful for women who have failed multiple IVF cycles, even after transferring good-quality embryos.

  • Mechanism of Action
  • Administration of IVIg Therapy
  • Clinical Uses of IVIg in IVF
  • Side Effects and Risks
  • Case Studies
  • Conclusion

Mechanism of Action

Mechanism of Action of Intravenous immunoglobulin (IVIg) therapy

Intravenous Immunoglobulin (IVIG) therapy is a treatment derived from pooled human plasma containing a broad spectrum of antibodies. The exact mechanism by which IVIg therapy works in immune-related infertility is not fully understood. However, several mechanisms have been proposed. IVIg contains a diverse array of antibodies that can target and neutralize autoantibodies or harmful immune cells, reducing their detrimental effects on pregnancy. It can also suppress the production of inflammatory cytokines and promote anti-inflammatory responses, creating a more favorable environment for implantation and pregnancy.

Administration of IVIg Therapy

IVIg therapy is administered through intravenous infusion. The dosage and frequency of treatment vary depending on the specific diagnosis, individual patient characteristics, and the healthcare provider’s treatment protocol. The infusion may take several hours, and patients are monitored closely during the procedure.

  1. Dosage: The usual dosage of IVIg for treating recurrent pregnancy loss is 25 grams. However, successful pregnancies have been reported with dosages ranging from 20 to 60 grams. The dosage may vary depending on individual circumstances and the specific immune factors involved.
  2. Frequency of Treatment: IVIg infusions are typically given every 28 days due to its half-life of 28 days in circulation. This means that the therapy remains effective for this duration. The treatment is usually continued for four to five monthly treatments in cases of first trimester pregnancy losses. For women with a history of late pregnancy losses, treatment may continue until 28 to 32 weeks of gestation.
  3.  Monitoring and Blood Tests: Throughout the treatment, pregnancies are monitored using immunologic blood tests. These tests help assess the immune response and determine the effectiveness of the therapy. Based on the results of these blood tests, the treatment plan may be modified as necessary.

It’s important to note that IVIg therapy is personalized to each individual’s medical history and specific circumstances. The dosage, frequency, and duration of treatment may vary based on the patient’s obstetric history and the recommendations of the healthcare provider. Regular monitoring and communication with the healthcare team are crucial for ensuring the best possible outcomes.

Would you like details on dosage, administration, or what are your chances of success rates using this therapy? Book a consultation with our fertility experts today

Clinical Uses of IVIg in IVF

Clinical Uses of Intravenous immunoglobulin (IVIg) therapy in IVF

    • For Recurrent Implantation Failure (RIF): Administered before embryo transfer to suppress harmful immune responses.

    • For Recurrent Pregnancy Loss (RPL): Given during early pregnancy to prevent miscarriage caused by immune system overactivity.

    • For Autoimmune-Related Infertility: Used when conditions like APS, Hashimoto’s, or elevated NK cells are diagnosed.

 

Side Effects and Risks

IVIg therapy is generally considered safe, but it carries potential risks and side effects. The most common side effects include headache, fever, chills, nausea, muscle aches, and fatigue. Allergic reactions can occur but are rare. There is also a risk of blood clot formation, especially in patients with a history of thrombosis. Therefore, it is crucial to closely monitor patients during and after IVIg infusion and take appropriate precautions.

Case Studies

Numerous case studies and small-scale research studies have explored the use of IVIg therapy in immune-related infertility. These studies have reported positive outcomes, particularly in patients with autoimmune disorders or antiphospholipid antibodies. For example, a study published in the Journal of Clinical Immunology demonstrated that IVIg therapy significantly reduced the incidence of miscarriage in patients with antiphospholipid antibodies. Another study published in Human Reproduction showed improved pregnancy outcomes in patients with unexplained infertility who received IVIg therapy.

Here are some links to studies on this therapy:

It is important to note that while case studies and small-scale research provide valuable insights, larger randomized controlled trials are needed to establish the efficacy and safety of IVIg therapy in immune-related infertility.

Conclusion

IVIg therapy is a form of immune therapy used to address immune-related factors in infertility.

IVIG therapy rebalances the immune system by suppressing harmful immune responses, reducing inflammation, and promoting embryo acceptance.

IVIg therapy aims to reduce the risk of immune-mediated pregnancy loss in patients with autoimmune disorders.

It is a promising treatment for women facing unexplained IVF failure, recurrent miscarriages, or immune-based infertility issues. However, its use should be carefully monitored to ensure the best outcomes

While it shows promise, the use of IVIg therapy should be determined on a case-by-case basis in consultation with a qualified reproductive immunology specialist.

Further research is needed to fully understand its efficacy, optimal dosage, duration of treatment, and potential side effects in the context of immune-related infertility.

 

Doctors