Becoming a parent is usually thought of as a natural part of life, yet for many couples, the process isn't that easy. You might have taken every test, monitored every cycle, and done every doctor's recommendation—only to be informed that everything is normal. And yet, conception still doesn't occur. This infuriating and most of the time perplexing experience has a name: unexplained infertility. In contrast to conditions in which the etiology is obvious, unexplained infertility puts couples hunting for answers in reproductive medicine's gray areas. Diagnosis is often both a blessing and a reversal—relief that nothing appears "wrong," but distress that no obvious solution exists.

For most couples, parenthood is a journey of anticipation, planning, and hope. But what is a couple to do when there are normal test results, no medical red flags found by doctors, and yet no pregnancy? This is the frustrating, emotionally draining experience of unexplained infertility—a condition which brings couples more questions than answers.

During an interview with Dr. R. Suchindra, Senior Consultant – Reproductive Medicine, Milann Fertility Hospital, Bengaluru, he states, "Unexplained infertility is when a couple fulfills all the clinical criteria for natural conception—normal ovulation, normal sperm, patent fallopian tubes, and harmonious hormones—still does not conceive after more than one year of attempting to conceive under age 35, or six months above."

This paradox, too often underemphasized in the discussion of fertility, plagues couples around the globe and is becoming a growing public health issue. Infertility itself affects approximately 10–15% of married couples in India, yet as much as 30% of those cases qualify as unexplained. And although the term may sound final, doctors point out it is really more a matter of limitations in testing than an absolute lack of causes.

Why "Unexplained" Infertility Doesn't Mean "Hopeless"?

The phrase "unexplained infertility" may sound daunting, but it's worth recognizing that it doesn't equal a guarantee of impossibility. Rather, it denotes the realm of reproductive science as of today. Physicians claim that the condition is undeservedly named. What appears to be unexplained now can, in the course of time, turn out to be due to minute hormonal variations, egg or sperm quality problems, or even molecular immune responses that current testing cannot possibly measure.

Dr. Suchindra adds that medical technology is a large contributor: "The more sophisticated the diagnostic equipment, the fewer couples are in the unexplained category. Sometimes the cause is just concealed, not missing."

This is an important point because it reinterprets unexplained infertility as an obstacle to overcome—not an impossible one.

Hidden Causes Behind Unexplained Infertility

Though there is no one explanation, studies propose a cluster of underlying factors that could be responsible:

Latent Tuberculosis (Genital TB): Especially in South Asian nations, this latent infection can destroy the endometrium or fallopian tubes without overt symptoms.

Endometriosis and Muted Hormonal Disturbances: Disorders such as endometriosis, insulin resistance, or thyroid disease are not necessarily detected through regular checks but are able to interfere with ovulation and implantation.

Nutritional Deficiencies and Autoimmune Conditions: Deficiencies in some vitamins and minerals, celiac disease, diabetes, or autoimmune diseases like lupus and antiphospholipid antibody syndrome (APS) may interfere with reproductive processes.

Cervical Mucus and Immunological Factors: In certain instances, cervical mucus has antibodies that destroy sperm, a condition referred to as immunological infertility.

Egg and Sperm Quality: Counts of eggs and sperm motility can be measured, but quality is more difficult to quantify. Unhealthy eggs or undetectable sperm defects might be undetectable in routine reports but affect conception.

All of this serves to explain why unexplained infertility is still such a difficult diagnosis—because the causes are usually hidden beneath the surface.

The Emotional Burden of an Invisible Diagnosis

For couples, a diagnosis of unexplained infertility is more than a medical diagnosis—it's a psychological odyssey. A lack of obvious explanation can be followed by cycles of self-blame, anxiety, and uncertainty. There is no one to draw a roadmap for treatment in this situation, as there might be for other conditions, and so patients can feel helpless.

Dr. Suchindra stresses, "This is usually the most difficult aspect for couples. With no cause found, they are left stuck. But here's what to understand: Many couples with unexplained infertility do end up conceiving naturally or with some assisted help."

Support, counseling, and honest communication with the healthcare providers become as crucial as treatments.

Approaches That Can Improve Chances of Conception

The lack of a definite cause doesn't imply there's no hope. Indeed, a combination of lifestyle changes, medical surveillance, and new reproductive technologies usually enhances the chances considerably.

1. The Importance of Time and Patience

On occasion, physicians will suggest a "watchful waiting" plan. Couples who are less than 35 years old can be told to keep trying naturally for several more months and monitor ovulation carefully. Research indicates that spontaneous conception is possible in a high percentage of situations once tension is minimized and timing is refined.

2. Lifestyle Changes That Enhance Fertility

Having a healthy weight, consuming a healthy diet, smoking cessation, reducing alcohol, reducing caffeine intake, and engaging in stress-reducing activities like yoga or mindfulness can provide a conducive environment for conception. While these measures don't "treat" infertility, they improve overall reproductive health.

3. Medical Treatments and Assisted Reproductive Technology (ART)

When waiting and lifestyle modifications are not sufficient, physicians might prescribe treatments like:

Ovulation stimulation with medication to control or enhance egg release.

Intrauterine Insemination (IUI), wherein thawed sperm is inserted directly into the uterus when timed properly.

In Vitro Fertilization (IVF), which circumvents most natural obstacles by fertilizing eggs externally and transferring embryos.

All of them have varying success rates based on the couple's age, health, and duration of trying.

Reproductive medicine is developing fast. Genetic testing, artificial intelligence for embryo choice, and better understanding of immunological and metabolic causes of infertility will soon render the "unexplained" status much less frequent.

"Each year we find new layers of how the body prepares for pregnancy," Dr. Suchindra explains. "Our challenge as clinicians is to bridge that gap between what we know and what remains unknown, so couples can find clarity and hope."

Unexplained infertility can be a disquieting diagnosis, but it is not an impasse. Many couples still conceive naturally after a few months of waiting, while others succeed by adjusting their lifestyle and by using ART. What this process requires most is resilience, honest communication with the medical team, and the knowledge that reproductive science is continuously evolving.

As Dr. Suchindra stresses, "The lack of an answer today does not equate to the lack of a solution tomorrow." To couples on this journey, that message can convert doubt into potential.

Squirrels could be natural hosts of the mpox virus (MPXV) -- that causes monkeypox disease -- according to a recent study by German researchers.

The team from the Helmholtz Institute for One Health (HIOH) identified the fire-footed rope squirrel (Funisciurus pyrropus) as a likely natural reservoir of the MPXV.

The study published in the journal Nature revealed that sooty mangabeys – a primate found in West Africa -- can contract mpox by eating infected squirrels. The disease may present mild lesions, but it can also cause more severe skin lesions or even be fatal.

"Identifying the animal sources of the virus and the exposure routes that lead to inter-species transmission are key steps towards understanding spillover mechanisms and developing effective prevention measures to mitigate the risk of transmission to humans," said Livia V. Patrono, one of the senior authors at HIOH.

Squirrels Suspected MPXV Hosts

While squirrels have long been suspected as potential reservoirs for MPXV, their role was confirmed after an investigation of an mpox outbreak among wild sooty mangabeys (Cercocebus atys) in Côte d'Ivoire.

During the outbreak, reported in early 2023, nearly one-third of the primates showed clinical signs of disease, and four infants died.

The team conducted viral genome sequencing and found that the infected monkeys carried a virus that was nearly identical to an MPXV strain identified in a fire-footed rope squirrel found dead 12 weeks earlier nearby.

Further, the team analyzed fecal samples from the mangabeys. A sample collected eight weeks before the outbreak's onset contained DNA from both the virus and the rope squirrel. This provided strong evidence of interspecies transmission at that moment.

Sooty mangabeys have been previously observed catching and eating fire-footed rope squirrels, which provide a direct route for the transmission of viruses.

Mpox Continues To Spread Globally

Although mpox is no longer a public health emergency, outbreaks of clade I and clade II strains of the mpox virus are continuing in many countries around the world, especially in Africa.

Last week, Madagascar announced the country's first death from mpox, a 3-year-old girl from the island nation’s eastern city of Toamasina.

The WHO has also confirmed that two cases of the recombinant strain – combining genomic elements of clades Ib and IIb of the monkeypox virus (MPXV) – have been identified to date: one in the United Kingdom and one in India.

Mpox is an infectious disease caused by the monkeypox virus (MPXV), part of the Orthopoxvirus genus, which also includes the virus that causes smallpox.

It spreads through close physical contact, including sexual contact, and in some cases through contaminated materials or respiratory droplets.

Symptoms typically include fever, swollen lymph nodes, rash, and/or lesions.

The global health body has also urged all countries to “remain alert to the possibility of MPXV genetic recombination.” It has also urged for continued epidemiological surveillance, sequencing, vaccination of at-risk groups, and infection prevention and control measures.

An international group of scientists has created an artificial intelligence tool that can estimate a woman’s likelihood of developing breast cancer within the next four years.

The AI tool, known as the BRAIx risk score, analyzes mammogram images to generate an individualized risk assessment and flag women who may face a higher chance of developing the disease.

It may not only show the current risk but also predict the future risk, enabling early detection and treatments for a better outcome.

According to the findings published in The Lancet Digital Health journal, nearly one in 10 women ranked in the top 2 percent of risk by the AI tool were diagnosed with breast cancer within four years. This was despite previously receiving a clear screening result.

“These risk scores enable future development of personalized screening pathways to transform population breast cancer screening and save lives,” said corresponding author Helen M. L. Frazer of the University of Melbourne.

Frazer noted that identifying women who appear cancer-free but carry very high risk -- comparable to those with inherited BRCA1 or BRCA2 mutations -- will unravel both hereditary and non-hereditary causes of breast cancer.

From one-size-fits-all screening to personalization

Breast cancer screening programs have significantly lowered mortality rates -- by roughly 40-50 percent among women aged 50 to 74. However, most screening systems still apply the same approach to all women, regardless of individual risk.

Traditional screening tools use genetics, breast density, and questionnaires to estimate breast cancer risk. On the other hand, new AI-based screening tools, such as BRAIx personalizes screening by gathering information already present in breast scan images to better identify who is at higher risk.

“Our results show that conventional mammographic density is a far weaker predictor of breast cancer risk than the BRAIx risk score, even for interval cancers,” the researchers said in the paper. Interval cancers are aggressive tumors diagnosed after a negative mammogram.

The BRAIx Tool

The BRAIx risk score was developed using mammograms from nearly 400,000 women. To prove its efficacy, the AI tool was tested on data from almost 96,000 women from Australia and then confirmed in an independent Swedish population of over 4,500 women.

The findings showed that:

• The BRAIx risk score estimated breast cancer risk more accurately than the traditional risk factors, such as breast density, country of birth, and even family history.

• For the top 2 percent of women with the highest BRAIx risk score, the probability of a cancer diagnosis within 4 years was 9.7 percent -- a risk level exceeding that typically seen in women with inherited BRCA1 or BRCA2 mutations.

The BRAIx risk score can:

• Make breast screening more personalised,
• Improve early cancer detection,
• Reduce false alarms,
• Save lives without increasing costs

Global Breast Cancer Burden

Breast cancer continues to be the most common cancer among women worldwide.

A recent study published in The Lancet Oncology journal predicted that the number of new cases of the deadly disease will reach more than 3.5 million globally in 2050 -- rising by a third from 2.3 million in 2023.

Annual deaths from the disease will also rise by 44 percent -- from around 764,000 to 1.4 million.

However, not smoking, getting sufficient physical activity, lowering red meat consumption, and having a healthy weight can help prevent over a quarter of healthy years lost to illness and premature death from breast cancer.

People who survived a COVID-19 infection can be at significant risk for kidney disease, acute kidney injury, and chronic kidney disease. compared to individuals who were not infected, according to a study.

The study, published online in the journal Communications Medicine, revealed that COVID patients have

• a 2.3-times higher risk of acute kidney injury
• a 1.4-times higher risk of chronic kidney disease
• a 4.7 times higher risk of kidney failure

“While we’re in the post-pandemic era, this shows that COVID-19 history is an important variable when considering the long-term impact of the infection on kidney function and disease,” said first author Yue Zhang, who was at Pennsylvania State University, US, while conducting the study. Zhang is currently a postdoctoral scholar at Johns Hopkins Bloomberg School of Public Health.

How Was The Study Conducted?

For the study, data on over 3 million working-age adults in the United States were analyzed.

The team compared the effect of influenza, another common viral infection that affects kidney health, and people with a history of COVID infection on kidney infections.

Using a machine learning model, the individuals were followed between 180 and 540 days for the emergence of new acute or sudden kidney disease.

The results showed that:

• Both COVID and the flu can worsen kidney health
• Flu caused a mild and temporary effect
• COVID increased the risk of acute kidney injury for a longer duration
• COVID survivors developed kidney disease within a few hours to a few days
• COVID patients had a longer-term chronic and end-stage kidney disease.

How COVID Worsens Kidneys Health

The Penn State researchers explained that kidney cells express high levels of the primary protein receptors that SARS-CoV-2 uses to enter and infect cells. Kidney cells also produce specialized enzymes that help viruses enter cells.

According to Kidney Health Australia, an acute COVID infection can impact the kidneys with fevers and respiratory symptoms, and/or worsening blood sugar control.

The US National Institutes of Health stated that renal dysfunction is an increasing clinical indicator of COVID propagation.

Citing several studies, the NIH said that the most common clinical manifestation is proteinuria -- found in more than half of the COVID patients. In addition, hematuria, elevated blood urea nitrogen, and elevated serum creatinine are other common features in Covid survivors with poor kidney health.

Nasr Ghahramani, Professor of Medicine at Penn State College of Medicine, stressed the need for COVID survivors, especially those with diabetes and high blood pressure, to take "more frequent and more prolonged monitoring of their kidney function" to enable early detection and better outcomes.