Exploring Lymphocyte Immunotherapy as a Treatment for Recurrent Miscarriage: A Case Study of Immune System Modulation and Positive Clinical Pregnancy Rate

ABSTRACT

This case study reviews the use of Lymphocyte Immunotherapy (LIT) in a 28-year-old female patient who had a history of recurrent first-trimester miscarriages and failed intracytoplasmic sperm injection (ICSI) cycles. She had good ovarian reserve, normal semen analysis, and negative autoimmune tests but experienced four early miscarriages, which suggested an immune-mediated issue. LIT was chosen as a treatment option to address the possibility of immune system dysregulation contributing to pregnancy loss. LIT is the process of infusing the husband’s lymphocytes to promote maternal tolerance of paternal antigens, reducing the possibility of immune foetal rejection. A received LIT was performed six weeks prior to a fresh ICSI cycle, with successful fertilization and transfer of embryos. There is evidence that positive outcomes occurred in serial ultrasounds and hormone levels at 6, 8, and 12 weeks with subsequent birth at term of a healthy baby. This case points to the possibility of using LIT as a therapeutic intervention in the treatment of unexplained recurrent miscarriage in patients who had previously failed previous assisted reproductive treatments. While the mechanism of action for LIT remains unknown, it would seem to somehow modulate the immune responses so that pregnancy results in better outcomes. This case may thus provide new evidence for LIT as a possible management strategy for those with immune causes of recurrent pregnancy loss (RPL) but warrants additional studies to optimize its use and effectivity.

INTRODUCTION

Pregnancy is considered a semi-allograft due to the expression of paternal antigens by the embryo, which can provoke an immune response in the mother. This immune dysregulation is thought to play a significant role in conditions such as repeated implantation failure and recurrent pregnancy loss (RPL). Lymphocyte Immunotherapy (LIT) has emerged as a promising approach to prevent pregnancy loss in these patients. Various mechanisms have been proposed to explain the effectiveness of LIT, including its ability to enhance the production of anti-paternal cytotoxic antibodies, which may help the maternal immune system better tolerate the pregnancy.[1] The aim of this study was to study perinatal outcome and determine risk factors for subsequent pregnancy loss in women with recurrent miscarriage who underwent LIT. The research was prospective: Infants and neonates are more prone to morbidity and mortality from infections of the lower respiratory tract than are older children.[2] One of the most distressing conditions related to infertility is RPL, which causes significant anxiety and concern for affected couples. RPL is defined in 2 to 5% of women during reproductive age that two or more losses of pregnancy after 20 weeks of gestation.[3]

CASE PRESENTATION

Patient information

A couple visited an infertility clinic in Wardha test tube baby center, Maharashtra. The woman, 28 years old, and the male, 31 years old, have been trying to conceive for 2 years but the female patient had 4 early miscarriages, all during the first trimester, after undergoing in vitro fertilization (IVF) and ICSI treatments. The couple was given a clear explanation of the treatment options, benefits, and risks. They both gave their consent to proceed with the treatment.

Medical/surgical history

The couple has not any surgical treatments in the past. The husband has no medical history, while the female patient was diagnosed with miscarriage through ultrasound. This was the first visit to the infertility clinic. She has previously undergone multiple fertility treatments, including six cycles of Clomiphene Citrate (CC) for ovulation induction, with no successful pregnancies. Additionally, she attempted two cycles of intrauterine insemination (IUI), both of which were unsuccessful. She has also undergone two IVF cycles, both of which ended in failure.

Physical examination

The normal range The Body mass index of female is 22 kg/m² and the BMI of the husband is 24 kg/m² which lie within representing a healthy individual. The semen analysis of male patient shows 85 mil/ml count, 80% motility and 5% normal morphology which reveals that the report is normal.

Investigation

Autoimmune testing includes a set of blood tests to check for underlying autoimmune disorders, such as antiphospholipid syndrome (APS) or systemic lupus erythematosus (SLE), which could cause repeated miscarriages. A test to check the activity of Natural Killer (NK) cells may also be done, as overactive NK cells can attack the embryo and lead to pregnancy loss. Hormonal tests are carried out to check the levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol, thyroid-stimulating hormone (TSH), and. Progesterone to ensure that the reproductive system is in good working condition before fertility treatment. The fallopian tubes and uterine cavity are also checked for any structural problems that may prevent successful implantation or cause early miscarriage. In repeated miscarriages, genetic testing, such as karyotyping, may be advised to check for any chromosomal issues that may be affecting pregnancy outcomes.

Dignostic treatment

As part of the immune-related infertility treatment plan, the patient was subjected to Lymphocyte Immunotherapy. The starting point of this process was from her male partner by taking a blood sample. The blood was taken from him in Solution A tube having anticoagulants inside so that the blood does not clot. He was then subjected to centrifugation at 3000 rpm for 30 min, dividing the sample into layers. The buffy coat, or the key layer containing the lymphocytes, was carefully withdrawn and placed into a Solution B tube. Again, it went through another 15 min of centrifugation [Figure 1]. After disposing of the liquid, what was left was the concentrated pellet of the lymphocytes. These cells were transferred into the Solution C tube, extracted and loaded into the syringe; from there they were ready to be infused into the patient by intravenous administration [Figure 2]. This process had been carefully designed to help adjust her immune system, promote tolerance, reduce rejection, and enhance the chances of successful implantation of an embryo and pregnancy. The treatment was performed on three sessions spaced four weeks apart as part of a larger plan to maximize her chances of conception through assisted reproductive technologies.

Figure 1.

Lymphocytes Immunization Theraphy (LIT) Used for patient

Figure 2.

Lymphocytes Immunization Theraphy (LIT) Transferred to the patient

Follow up

The embryo transfer was performed after LIT therapy and at 14 days, the serum βHCG test result was positive. For monitoring the early pregnancy an ultrasound at six weeks confirmed that it was an intrauterine pregnancy with the presence of fetal heartbeat. The second ultrasound was conducted at Eight weeks where baby growth was confirmed to be normal. A healthy pregnancy scan without any miscarriage signs was found at 12 weeks. It remained stable following monitoring through various ultrasounds and hormone tests during the periods leading up until the second trimester of her pregnancy.

DISCUSSION

This case highlights the potential role of LIT in treating recurrent miscarriage and failed assisted reproduction. Immune system dysregulation is thought to contribute to pregnancy loss, especially when there is no clear cause. The effectiveness of LIT in addressing RPL due to all no immunity has been a topic of ongoing debate for years.[4] LIT aims to reduce maternal immune rejection of the foetus by promoting tolerance to paternal antigens. In this case, prior to LIT, the patient had experienced multiple miscarriages despite successful fertilization via ICSI, indicating a potential underlying immune-mediated issue that could not be identified through conventional testing. LIT changes the proportions and functions of many peripheral blood lymphocyte subsets. Some of these changes may prove beneficial for pregnancy maintenance, whereas others could represent potential markers to predict subsequent pregnancy loss.[5]

CONCLUSION

This case demonstrates the effectiveness of LIT in improving pregnancy outcomes for women with recurrent miscarriages and failed ICSI cycles. The therapy helped modulate the immune response, which appeared to be a significant factor in previous pregnancy losses. After the intervention, the female patient successfully carried a pregnancy to term, highlighting the potential for LIT to address immune factors contributing to recurrent pregnancy loss. While LIT offers promising results, it remains essential for further studies and clinical trials to confirm its efficacy and refine its use in the management of recurrent miscarriage and infertility.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Conflicts of interest

There are no conflicts of interest.

Funding Statement

Nil.