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Infertility

Disease Details

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Description: Infertility is the inability to conceive a child after 12 months of regular, unprotected intercourse.
Type: Infertility itself is a condition rather than a single disease, and it can result from various causes including genetic factors. When infertility is influenced by genetics, it can be transmitted in several ways:

1. **Autosomal Dominant Inheritance:** Only one copy of the altered gene from either parent can cause infertility.
2. **Autosomal Recessive Inheritance:** Both parents must carry and pass on a copy of the mutated gene for the offspring to be affected.
3. **X-linked Inheritance:** The gene causing infertility is located on the X chromosome, and the pattern of inheritance differs between males and females.
4. **Multifactorial Inheritance:** Involves a combination of multiple genes and environmental factors.

The specific type of genetic transmission depends on the underlying genetic cause of infertility. Examples include mutations in genes like CFTR (associated with cystic fibrosis and male infertility) or chromosomal abnormalities such as Klinefelter syndrome (47,XXY).
Signs And Symptoms: ### Signs and Symptoms of Infertility

#### Women:
- Irregular or absent menstrual cycles
- Painful periods (dysmenorrhea)
- Hormonal fluctuations causing symptoms like acne, hair growth, or weight gain
- Pelvic pain
- Symptoms of underlying conditions such as endometriosis or polycystic ovary syndrome (PCOS)

#### Men:
- Problems with sexual function (e.g., difficulty with ejaculation or erectile dysfunction)
- Pain, swelling, or a lump in the testicle area
- Decreased facial or body hair or other signs of a chromosomal or hormonal abnormality
- Lower than normal sperm count

Both men and women should consult a healthcare provider if they have been unable to conceive after one year of regular, unprotected intercourse, or after six months if the woman is over 35.
Prognosis: The prognosis for infertility varies widely depending on underlying causes, age, health condition, and treatments available. Many individuals or couples may achieve pregnancy with appropriate intervention, such as medications, surgery, assisted reproductive technologies like in vitro fertilization (IVF), or lifestyle changes. For others, it may be more challenging, and some might explore alternatives like adoption or surrogacy. Early diagnosis and treatment typically improve the chances of a successful outcome.
Onset: The onset of infertility refers to the point at which a couple first experiences difficulty conceiving after a period of regular, unprotected intercourse. For women, this concern typically arises after 12 months of trying to conceive if they are under 35 years old, or after 6 months if they are 35 or older. For men, infertility can be identified at a comparable timeframe in conjunction with the woman’s difficulty conceiving, often leading to an evaluation of both partners.
Prevalence: Infertility affects approximately 15% of couples globally. It is a common condition where couples are unable to conceive after one year of unprotected intercourse. Both men and women can contribute to infertility, with factors including age, lifestyle, medical conditions, and reproductive system disorders.
Epidemiology: Prevalence of infertility varies depending on the definition, i.e. on the time span involved in the failure to conceive.

Infertility rates have increased by 4% since the 1980s, mostly from problems with fecundity due to an increase in age.
Fertility problems affect one in seven couples in the UK. Most couples (about 84%) who have regular sexual intercourse (that is, every two to three days) and who do not use contraception get pregnant within a year. About 95 out of 100 couples who are trying to get pregnant do so within two years.
Women become less fertile as they get older. For women aged 35, about 94% who have regular unprotected sexual intercourse get pregnant after three years of trying. For women aged 38, however, only about 77%. The effect of age upon men's fertility is less clear.
In people going forward for IVF in the UK, roughly half of fertility problems with a diagnosed cause are due to problems with the man, and about half due to problems with the woman. However, about one in five cases of infertility have no clear diagnosed cause.
In Britain, male factor infertility accounts for 25% of infertile couples, while 25% remain unexplained. 50% are female causes with 25% being due to anovulation and 25% tubal problems/other.
In Sweden, approximately 10% of couples wanting children are infertile. In approximately one-third of these cases the man is the factor, in one third the woman is the factor, and in the remaining third the infertility is a product of factors on both parts.
In many lower-income countries, estimating infertility is difficult due to incomplete information and infertility and childlessness stigmas.
Data on income-limited individuals, male infertility, and fertility within non-traditional families may be limited due to traditional social norms. Historical data on fertility and infertility is limited as any form of study or tracking only began in the early 20th century. Per one account, "The invisibility of marginalised social groups in infertility tracking reflects broader social beliefs about who can and should reproduce. The offspring of privileged social groups are seen as a boon to society. The offspring of marginalised groups are perceived as a burden."
Intractability: Infertility can be challenging to treat, but it is not generally considered intractable. Many underlying causes of infertility can be addressed with medical interventions, lifestyle changes, or assisted reproductive technologies such as in vitro fertilization (IVF). Success rates vary depending on factors such as age, underlying health conditions, and the specific cause of infertility. While some cases may be difficult to treat, many individuals and couples do achieve successful pregnancies with appropriate intervention.
Disease Severity: Infertility is typically not classified by severity in the same manner as many other diseases because it represents the inability to conceive after a year of regular, unprotected intercourse rather than varying degrees of a single illness. The underlying causes of infertility can vary widely in terms of severity and complexity, and they include factors such as hormonal imbalances, structural abnormalities, genetic conditions, and lifestyle factors. Each case is unique and often requires personalized evaluation and treatment.
Healthcare Professionals: Disease Ontology ID - DOID:5223
Pathophysiology: Infertility involves complex pathophysiology that can affect both males and females. In females, it may be caused by ovulation disorders (e.g., polycystic ovary syndrome, premature ovarian failure), fallopian tube damage or blockage, endometriosis, uterine conditions (e.g., fibroids), or hormonal imbalances. In males, infertility often stems from issues such as low sperm production, abnormal sperm function, or blockages that prevent sperm delivery. Genetic factors, systemic diseases (e.g., diabetes), lifestyle factors (e.g., smoking, alcohol use), and environmental exposures can impact both sexes. Infertility can result from a combination of these factors, making diagnosis and treatment complex.
Carrier Status: Infertility is a condition that affects both men and women and can have various underlying causes. While "carrier status" typically refers to the presence of genetic mutations that can be passed on to offspring, infertility itself is not generally described in terms of carrier status. However, certain genetic conditions that may be inherited could contribute to infertility. Detailed genetic screening and consulting with a healthcare professional can help identify if there are genetic factors involved in a specific case of infertility.
Mechanism: Infertility is a complex condition with various potential mechanisms. Here's a brief overview:

### Mechanisms
Infertility can be due to factors affecting either or both partners.

1. **Male Factors**:
- **Sperm Production Disorders**: Low sperm count (oligospermia), poor sperm quality, or absence of sperm (azoospermia).
- **Structural Issues**: Blockages or obstructions in the reproductive tract, preventing sperm delivery.
- **Functional Problems**: Erectile dysfunction or issues with ejaculation.

2. **Female Factors**:
- **Ovulatory Disorders**: Irregular or absent ovulation, often due to polycystic ovary syndrome (PCOS) or hormonal imbalances.
- **Tubal Factors**: Blocked or damaged fallopian tubes due to infections, surgery, or conditions like endometriosis.
- **Uterine/Cervical Factors**: Abnormalities in the uterus or cervix affecting implantation or sperm transport.

### Molecular Mechanisms
Several molecular mechanisms underpin infertility, often involving hormonal, genetic, or cellular dysfunction:

1. **Hormonal Regulation**:
- **Hypothalamic-Pituitary-Gonadal (HPG) Axis**: Dysregulation in the release of GnRH, LH, or FSH can impair gamete production and reproductive function.
- **Androgen and Estrogen Receptors**: Mutations or polymorphisms in hormone receptors can affect spermatogenesis or folliculogenesis.

2. **Genetic Factors**:
- **Chromosomal Abnormalities**: Klinefelter syndrome (XXY), Turner syndrome (X0), and other aneuploidies can impact gamete production.
- **Gene Mutations**: Mutations in genes like CFTR (linked to cystic fibrosis and congenital absence of the vas deferens) or NR5A1 (involved in steroidogenesis) can result in infertility.

3. **Molecular Pathways**:
- **Oxidative Stress**: Imbalance in reactive oxygen species (ROS) and antioxidants can damage sperm DNA or impair oocyte quality.
- **Apoptosis**: Dysregulated apoptosis in the testes or ovaries can lead to reduced gamete viability.

4. **Immune Factors**:
- **Autoimmunity**: Autoimmune reactions against gametes or reproductive tissues can interfere with fertility.
- **Inflammatory Cytokines**: Elevated levels of inflammatory cytokines can affect sperm motility, oocyte quality, or endometrial receptivity.

Understanding the intricate mechanisms of infertility involves a combination of genetic, hormonal, and environmental factors, and ongoing research aims to elucidate these pathways to provide better diagnostic and therapeutic strategies.
Treatment: Treatment depends on the cause of infertility, but may include counselling, fertility treatments, which include in vitro fertilization. According to ESHRE recommendations, couples with an estimated live birth rate of 40% or higher per year are encouraged to continue aiming for a spontaneous pregnancy. Treatment methods for infertility may be grouped as medical or complementary and alternative treatments. Some methods may be used in concert with other methods. Drugs used for both women and men include clomiphene citrate, human menopausal gonadotropin (hMG), follicle-stimulating hormone (FSH), human chorionic gonadotropin (hCG), gonadotropin-releasing hormone (GnRH) analogues, aromatase inhibitors, and metformin.
Compassionate Use Treatment: Compassionate use treatments, off-label use, and experimental treatments are options available for managing infertility under specific circumstances.

1. **Compassionate Use Treatment**:
- This refers to the use of investigational drugs or therapies outside of clinical trials for patients with serious or life-threatening conditions when no satisfactory alternatives are available.
- For infertility, this might include access to certain advanced reproductive technologies or medications that are still under investigation but show promise in preliminary studies.

2. **Off-Label Treatments**:
- Off-label use involves prescribing approved medications or treatments for an indication not specified in the FDA approval.
- In infertility, drugs like letrozole (approved for breast cancer) may be used off-label to induce ovulation.
- Another example is the use of low-dose aspirin or metformin (typically used for diabetes) in specific infertility cases.

3. **Experimental Treatments**:
- These are treatments currently undergoing clinical trials and have not yet received regulatory approval.
- Techniques like ovarian tissue freezing and transplantation, uterine transplants, or advanced gene editing methods are considered experimental.
- Patients may choose to participate in clinical trials to access such treatments, which can be found through registries like ClinicalTrials.gov.

It is critical to discuss these options with a healthcare provider to understand the benefits, risks, and ethical considerations.
Lifestyle Recommendations: Lifestyle recommendations for managing infertility include:

1. **Maintain a Healthy Weight**: Both underweight and overweight conditions can affect fertility. Aim for a balanced diet and regular exercise.

2. **Quit Smoking**: Smoking can reduce fertility in both men and women. Quitting can improve reproductive health.

3. **Limit Alcohol Consumption**: Excessive alcohol intake can negatively impact fertility. It's best to limit or avoid alcohol while trying to conceive.

4. **Reduce Caffeine Intake**: High caffeine consumption may be linked to decreased fertility. Limit caffeine to less than 200-300 mg per day.

5. **Manage Stress**: Chronic stress can affect fertility. Techniques such as yoga, meditation, and deep-breathing exercises can help manage stress levels.

6. **Avoid Exposure to Toxins**: Minimize exposure to environmental pollutants, pesticides, and chemicals that can impact reproductive health.

7. **Exercise Moderately**: While regular physical activity is beneficial, excessive exercise can disrupt ovulation in women and reduce sperm count in men.

8. **Get Adequate Sleep**: Aim for 7-9 hours of sleep per night to help maintain hormonal balance.

9. **Monitor Ovulation**: For women, tracking ovulation can help in timing intercourse for conception.

10. **Seek Medical Advice**: If lifestyle changes do not help, consulting a healthcare provider for further evaluation and treatment options is recommended.
Medication: Medications commonly prescribed for infertility include:

1. Clomiphene Citrate (Clomid): Stimulates ovulation.
2. Letrozole (Femara): Often used for women with polycystic ovary syndrome (PCOS).
3. Metformin: Improves insulin resistance, commonly used in PCOS cases.
4. Gonadotropins: Includes FSH and LH injections to directly stimulate the ovaries.
5. Bromocriptine: Used for treating high prolactin levels.
6. Human Chorionic Gonadotropin (hCG): Triggers ovulation.
7. Cabergoline: Another medication for high prolactin levels.

Each treatment depends on the underlying cause of infertility.
Repurposable Drugs: Repurposable drugs that have been investigated for infertility include:

1. **Metformin**: Originally used for type 2 diabetes, metformin has shown efficacy in improving ovulation in women with polycystic ovary syndrome (PCOS).
2. **Clomiphene Citrate**: Although primarily used as a fertility drug, it was initially developed for breast cancer treatment.
3. **Letrozole**: Originally an aromatase inhibitor for breast cancer, letrozole is now used off-label to induce ovulation in women with infertility.

If "nan" refers to something specific, please provide additional context for clarification.
Metabolites: Infertility can be influenced by various metabolites, which are small molecules involved in metabolism. These metabolites can affect hormonal balance, oxidative stress, and overall reproductive health. Some key metabolites associated with reproductive processes include:

1. **Amino Acids**: Essential for hormone production and gamete quality.
2. **Lipids**: Involved in hormone synthesis and cell membrane structure.
3. **Reactive Oxygen Species (ROS)**: Elevated levels can cause oxidative stress, damaging reproductive cells.
4. **Glucose**: Critical for energy production in gametes and embryos.

Changes in these metabolites can disrupt normal reproductive functions and contribute to infertility.
Nutraceuticals: Nutraceuticals refer to food-derived products that offer health benefits, including supplements, fortified foods, and dietary products. Here are some commonly studied nutraceuticals that may have a positive impact on fertility:

1. **Folic Acid:** Vital for DNA synthesis and repair, crucial for cellular division and growth, often recommended for women trying to conceive.
2. **Coenzyme Q10 (CoQ10):** Known for its antioxidant properties, it may improve egg quality and sperm motility.
3. **Omega-3 Fatty Acids:** Found in fish oil, they are believed to enhance egg quality and reduce inflammation.
4. **Vitamin D:** Essential for hormone regulation, and there is some evidence linking adequate levels to improved fertility outcomes.
5. **Antioxidants (e.g., Vitamins C and E):** Help reduce oxidative stress, which can damage eggs and sperm.
6. **Inositol:** Particularly useful for women with polycystic ovary syndrome (PCOS), helping to regulate menstrual cycles and improve ovulatory function.
7. **L-Arginine:** An amino acid that may improve blood flow to the reproductive organs.

It's important to consult a healthcare provider before starting any nutraceuticals for fertility, as individual needs and conditions vary.
Peptides: The term "peptides" in the context of infertility refers to short chains of amino acids that play various roles in the body, including hormonal regulation and cell signaling. Some peptides, such as gonadotropin-releasing hormone (GnRH), are crucial in the regulation of reproductive hormones and can be used in treatments for certain infertility issues.

Nanotechnology (abbreviated as "nan") in fertility treatment explores the use of nanoparticles for targeted drug delivery, improving the effectiveness of medications and reducing side effects. This advanced approach is still largely in the research phase, but it holds promise for enhancing the precision and success rates of infertility treatments.