What is unexplained infertility and how is it diagnosed?

Infertility can be emotionally and physically overwhelming, particularly when no identifiable medical reason explains the inability to conceive. For many couples, receiving a diagnosis of unexplained infertility can be one of the most frustrating experiences when every test, scan, and evaluation appears normal, yet pregnancy continues to remain out of reach.

At ICPRM, specialists in reproductive immunology go beyond conventional fertility assessments to uncover the deeper biological and immune factors that may be affecting conception. By investigating subtle immune interactions and cellular mechanisms often missed in standard evaluations, ICPRM provides a more comprehensive understanding of each couple’s fertility challenges, paving the way for precise, evidence-based treatment solutions.

Understanding Unexplained Infertility

Unexplained infertility is diagnosed when a couple has been trying to conceive for at least a year (or six months for women over 35) and all routine fertility evaluations show normal results. In such cases, the reproductive organs, ovulation patterns, hormonal balance, and semen parameters appear normal, yet conception remains elusive.

This condition affects nearly 10–15% of infertile couples, making it one of the most perplexing challenges in reproductive medicine. While conventional tests may label it as “unexplained,” advanced diagnostic tools and reproductive immunology studies often uncover subtle immune causes of infertility that standard assessments fail to detect.

Common Causes of Unexplained Infertility

Although termed “unexplained,” several hidden biological and immune-related factors can interfere with conception and implantation. Some of the causes of unexplained infertility include:

• Immunological factors: The woman’s immune system may produce antibodies that attack sperm, embryos, or placental cells, leading to implantation failure or early pregnancy loss.
• Subtle ovulatory issues: Hormonal fluctuations or poor egg quality, even with regular cycles, can affect fertilization.
• Sperm DNA fragmentation: Standard semen analysis may not reveal microscopic DNA damage that prevents embryo development.
• Endometrial receptivity issues: The uterine lining might not be optimally prepared for implantation despite appearing normal on scans.
• Embryo-uterine interaction problems: Immunological incompatibility between the mother’s and father’s genetic material can result in failed implantation or miscarriage.

The Role of Reproductive Immunology

Reproductive immunology focuses on understanding how the immune system influences fertility and pregnancy outcomes. At ICPRM, specialists investigate immune causes of infertility using advanced testing to identify abnormalities in immune cell function, antibody levels, and genetic compatibility between partners.

Through this approach, conditions such as allo-immune infertility, repeated implantation failure, or IVF failure reasons can be properly diagnosed and treated. Addressing immune dysfunctions early helps prevent repeated failed cycles and improves overall success rates in both natural and assisted conception.

How Is Unexplained Infertility Diagnosed?

Diagnosing unexplained infertility requires a systematic and comprehensive evaluation of both partners to rule out identifiable causes such as hormonal imbalances, structural abnormalities, or sperm-related issues. At ICPRM, fertility experts follow a step-by-step diagnostic approach that combines standard fertility testing with advanced reproductive immunology assessments to reveal underlying immune or cellular factors that may affect conception.

1. Standard Fertility Testing

The initial phase of diagnosis involves conventional fertility testing to assess reproductive health and function in both partners.

• Ovulation and Hormone Testing:
  Blood tests are conducted to monitor hormone levels such as FSH, LH, AMH, prolactin, and thyroid hormones. These determine whether ovulation occurs regularly and if the ovaries are functioning normally. Hormonal imbalances, even subtle ones, can impact egg quality and timing of ovulation.
• Ultrasound Imaging:
  Transvaginal ultrasounds are used to evaluate the uterus and ovaries. This helps identify any abnormalities such as fibroids, cysts, or polyps that could interfere with implantation or embryo growth. Ultrasound also helps track follicle development during the ovulatory phase.
• Semen Analysis:
  For the male partner, semen analysis is performed to assess sperm count, motility (movement), morphology (shape), and vitality. Even when these parameters fall within normal ranges, deeper sperm function tests may sometimes be necessary to identify microscopic or DNA-level issues.
• Tubal Patency Tests:
  Procedures like Hysterosalpingography (HSG) or Sonohysterography are done to check whether the fallopian tubes are open and functioning properly. Blocked or damaged tubes can prevent the sperm and egg from meeting, leading to infertility.

If all these results appear normal, but pregnancy still does not occur, the couple is typically diagnosed with unexplained infertility. However, at ICPRM, this is not seen as the end of the diagnostic journey. It’s a signal to investigate deeper.

2. Advanced Reproductive Immunology Testing

Traditional fertility tests often overlook the role of the immune system in conception and implantation. This is where reproductive immunology provides critical insights. At ICPRM, advanced immune-based evaluations are performed to detect hidden causes that may interfere with pregnancy.

• NK (Natural Killer) Cell Activity Tests:
  These tests assess the number and activity level of NK cells, immune cells that, when overactive, may attack the embryo or hinder implantation. Abnormal NK cell activity has been linked to recurrent miscarriages and IVF failure.
• HLA Crossmatch:
  This test evaluates the presence of protective or blocking antibodies in the female that help safeguard the pregnancy. A lack of these protective antibodies may prevent successful implantation or lead to early miscarriage.
• Autoantibody Screening:
  Autoantibodies are immune proteins that mistakenly attack the body’s own cells, including reproductive tissues. Screening for antiphospholipid antibodies, antinuclear antibodies (ANA), and thyroid antibodies helps identify allo-immune factors that may be preventing conception.
• Cytokine Profiling:
  Cytokines are signaling proteins that regulate immune responses. An imbalance between pro-inflammatory and anti-inflammatory cytokines can negatively affect implantation. Profiling these markers helps tailor treatment strategies to restore immune balance.

3. Integrating the Results for a Targeted Approach

By combining findings from conventional and advanced immunological tests, ICPRM specialists create a comprehensive fertility profile for each couple. This approach allows for a more accurate identification of hidden causes and guides personalized fertility treatment for unexplained infertility, such as immunotherapy, hormonal correction, or IVF with immune support.

Through this detailed diagnostic process, ICPRM ensures that unexplained infertility is no longer left without answers, transforming uncertainty into clear, evidence-based direction for achieving a successful pregnancy.

Fertility Treatment for Unexplained Infertility

At ICPRM, the best fertility treatment for unexplained infertility is determined based on the couple’s immune and reproductive profile. Common approaches include:

• Targeted immunotherapy to correct immune system dysfunctions
• Lymphocyte Immunization Therapy (LIT) or ImmuLIT® to promote maternal immune tolerance
• Passive immunomodulatory medications to enhance implantation rates
• Prevent miscarriages after the active immunomodulation with ImmuLIT ®

This holistic, science-driven approach addresses both visible and hidden barriers to conception, significantly improving outcomes for couples who have previously experienced IVF failures or recurrent pregnancy loss.

Why Choose ICPRM for Unexplained Infertility?

At ICPRM, every case of unexplained infertility is managed by a multidisciplinary team led by Dr. Mugdha Raut and Dr. Mohan Raut, pioneers in reproductive immunology and fertility treatment. Their extensive clinical experience and advanced diagnostic approach enable precise identification of underlying immune or cellular factors that standard evaluations often miss. Each treatment plan is designed around the couple’s unique reproductive and immunological profile, ensuring a personalized, evidence-based pathway to conception.

One of ICPRM’s key innovations, ImmuLIT®, plays a transformative role in managing immune-related infertility and IVF failure reasons. As an advanced form of Lymphocyte Immunization Therapy, ImmuLIT® helps modulate the maternal immune system, improving embryo acceptance and implantation success. This therapy, combined with ICPRM’s specialized diagnostic tools and individualized care protocols, has helped countless couples overcome unexplained infertility and achieve healthy pregnancies after years of unsuccessful attempts.

Final Thoughts

Unexplained infertility does not imply the absence of a cause. It often highlights the limitations of conventional diagnostic methods. Many couples experience normal test results yet continue to face conception challenges due to subtle biological or immune factors that remain undetected through standard evaluations. By integrating advanced reproductive immunology and cellular-level analysis, these hidden issues can finally be identified and addressed with greater precision, offering couples a clearer understanding of their fertility journey.

For those struggling to conceive despite normal investigations or repeated IVF failures, the team at ICPRM provides a comprehensive, research-driven approach to care. Through personalized diagnostics and innovative therapies such as ImmuLIT®, ICPRM offers targeted fertility treatment for unexplained infertility, helping couples move beyond uncertainty toward renewed confidence and the possibility of a successful, healthy pregnancy.