For those struggling with Recurrent Pregnancy Loss (RPL), multiple miscarriages, or recurrent implantation failure, finding the root cause can be challenging. In this blog, we discuss the case of a 35-year-old patient who experienced five miscarriages over two years. Despite undergoing various standard fertility treatments and numerous consultations, she was ultimately given a diagnosis of ''unexplained infertility''.

"I felt helpless, I just couldn’t understand why this kept happening. I knew there had to be a solution, but finding it was like hitting a wall."

In search of answers and before proceeding with any treatments, the patient opted for advanced diagnostic options at Fertilysis, under the guidance of Dr. Venieratos. She underwent the Fertilysis RPL Test, a comprehensive panel covering two key areas in the investigation of unexplained infertility: Reproductive Immunology and the Microbiome. The test revealed a high-risk autoimmunity dysfunction, with elevated levels of cytotoxic NK cells and a dominant pro-inflammatory Th1 response, both considered risk factors for reproductive immunopathology. This includes conditions like recurrent spontaneous abortions (RSA), idiopathic infertility, and implantation failure in both natural and assisted reproduction attempts. A reduced Treg population may fail to suppress the pro-inflammatory Th1 response, hindering the embryo's ability to avoid maternal immune rejection. Additionally, a high-risk alloimmunity dysfunction was detected due to a partial HLA-DQα match between her and her partner. This 50% feto-maternal match is linked to reproductive immunopathology, such as idiopathic infertility and implantation failure in both natural and assisted conception efforts. The microbiome testing also showed a high-risk aerobic dysbiosis, with low levels of Lactobacilli in both the endometrial (menstrual blood) and vaginal swab samples, along with increased growth of opportunistic Staphylococcus spp. and Enterobacteriaceae.

• Endometrial & Vaginal Microbiome Testing: The test checks for a broad range of bacterial infections, yeast, STDs and viruses, ensuring a detailed assessment of the female reproductive tract. Endometritis, Vaginitis & Silent/Chronic infections causing microbiome dysbiosis, have been strongly associated with infertility, RIF, RPL, chemical pregnancies and serious complications of the 2nd & 3rd trimesters.
• Immune System Response: A significant portion of recurrent pregnancy loss is linked to immunological issues. The test checks for immune responses that could interfere with implantation or lead to embryo rejection.

Based on these findings, the patient’s treatment plan was multifaceted:

1. An effective antibiotic treatment protocol for Staphylococcus spp. and Enterobacteriaceae (e.g., Amoxicillin & Clavulanic acid), and the use of vaginal and oral female flora probiotics, to rebuild her Lactobacilli levels and restore her normal flora, as well as oral probiotics for her GI flora. Preventive use of vaginal antifungal cream in parallel to her treatment to prevent antibiotic-induced thrush was also recommended.
2. Based on her Reproductive Immunology Results, immune-modulating treatments were recommended. Options such as Lymphocyte Immunization Therapy (LIT) aim to optimize the balance of immune responses, reduce the mother’s immune system aggresiveness and promote a more favorable environment for pregnancy.

Lymphocyte Immunization Therapy (LIT) is an immunotherapy treatment specifically designed for women dealing with unexplained infertility or recurrent pregnancy loss. LIT aims to enhance the immune system’s ability to tolerate an embryo, reducing the risk of immune rejection. Under normal situation, the immune system should allow for the fetus to grow, even though half of its genetic material comes from the father. In this patient's case, her immune system wasn’t recognizing the fetus as non-threatening, leading to miscarriage. 

LIT involves injecting paternal antigens (from the father) into the prospective mother to "adapt" her immune system to the paternal proteins of the embryo.

This process helps to prevent the maternal immune system from "attacking" the embryo.

LIT works by:

• Stimulating the production of antibodies that block the maternal immune system from recognizing paternal HLA antigens.

• Reducing NK cell activity may attack the fetus.

• Shifting the immune response towards a pregnancy-friendly balance, increasing Treg responses that protect the embryo.

While LIT is considered experimental and is not FDA-approved, multiple studies have shown promising results. A meta-analysis published in the American Journal of Reproductive Immunology demonstrated a 45% increase in live birth rates for women undergoing LIT compared to those receiving placebo treatments. The patient’s decision to move forward with LIT as Fertilysis recommended, coupled with careful monitoring, was a crucial step toward finally achieving her dream.

Patient’s LIT treatment consisted of 4 rounds of LIT shots. The treatment plan was carefully tailored to her fertility history and immune profile. Sessions were scheduled at regular intervals before and during pregnancy to ensure the best possible outcome.

1. Initial Priming Sessions: Injections administered prior to pregnancy to build maternal immune tolerance.
2. Booster Sessions: Conducted at key stages of early pregnancy, including confirmation of a heartbeat (6-8 weeks) and after the nuchal translucency scan (11-14 weeks).
3. Continuous Monitoring: Regular checks of immune markers such as NK cells, T-reg cells, and cytokine ratios to track progress. After several months of treatment and another positive pregnancy test, the patient is due in December.

"When I heard the heartbeat for the first time at 8 weeks, I couldn’t believe it. I had never made it this far before," the patient shared with our customer care team. "LIT was the missing piece of the puzzle for me."

This patient’s story is one of resilience and hope where she found success through advanced testing and immunotherapy. The Fertilysis RPL test helped reveal underlying issues, and Lymphocyte Immunization Therapy (LIT) provided the immune system support she needed to maintain a healthy pregnancy. If you’re experiencing recurrent pregnancy loss or unexplained infertility, consider taking the first step towards understanding your fertility challenges. Schedule a consultation with Fertilysis and Dr Venieratos and start exploring your options!