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Infertility

Infertility is a serious medical, social and demographic problem. It’s a condition that affects millions of couples around the world, preventing them from pursuing their dreams of parenthood. Understanding the nature of infertility, its causes, and the available methods of diagnosis and treatment is crucial for people struggling with this challenge.

Definition of Infertility according to the WHO

The World Health Organization (WHO) defines infertility as the inability to get pregnant for a period of 12 months of regular sexual intercourse (on average 2-4 times a week), without the use of any contraceptive methods. This one-year period of unsuccessful efforts is widely recognized as the moment when a couple should consider starting diagnostics to determine the potential causes of fertility problems. It is worth noting that in healthy couples, the chance of getting pregnant in a single menstrual cycle is about 20-25% , and about 80% of couples achieve pregnancy within the first year of trying.

However, this standard 12-month diagnostic period is not an absolute rule. In the case of women over 35 years of age, and especially after 40 years of age, it is recommended to start diagnostics earlier, often after 6 months of unsuccessful attempts. This is due to the fact that a woman’s fertility significantly decreases with age, and time becomes a key factor in effective treatment. Thus, the WHO definition is an important diagnostic threshold, but it should be interpreted in the context of individual risk factors, such as the age of the partner.

Infertility as a Disease

The WHO classifies infertility as a disease , often referred to as a social disease due to its widespread prevalence and impact on society, the problem of infertility affects an increasing number of couples. This is also reflected in the international classification of diseases ICD-10, where male infertility has the code N46 and female infertility is N97. Recognizing infertility as a disease has significant consequences. First, it legitimizes seeking medical help and treating the problem as a condition that requires diagnosis and treatment, not just a personal failure. Secondly, it affects social perception and may open the way to systemic support, e.g. in the form of reimbursement of treatment.

However, this classification is not without controversy. Some argue that infertility does not fit into the traditional model of the disease because it does not cause physical pain (although it can be associated with painful conditions such as endometriosis), is not directly life-threatening and affects a couple rather than a single person. On the other hand, its enormous impact on physical, mental and social well-being is emphasized, limiting the possibility of fulfilling fundamental life desires and parental roles. This debate highlights the complex, bio-psycho-social nature of infertility that goes beyond the simple biomedical model.

Infertility Statistics

Infertility is a global problem. According to a 2023 WHO report covering data from 1990 to 2021, about 17.5% of the world’s adult population, or roughly 1 in 6 people, struggle with infertility. It is estimated that this problem affects between 60 and 80 million couples worldwide. In developed countries, the percentage of couples affected by infertility in childbearing age is 10-16%, which indicates the need for gynecological diagnosis and treatment of infertility. Secondary infertility is more common in developing countries, which is often associated with a higher incidence of sexually transmitted diseases and limited access to healthcare.

In Poland, estimates indicate that between 1 and 1.5 million couples struggle with infertility, which is about 15-20% of the population of reproductive age. Although the exact data for Polish may be incomplete , and some sources give slightly lower estimates (e.g. 9-14%), it is generally assumed that the problem affects one in five pairs. The scale of the problem is therefore enormous. Importantly, although the incidence of infertility in Poland is comparable to the European average, the availability and use of modern treatment methods, such as assisted reproductive technologies, still lags behind Western European countries. This may indicate systemic, financial or socio-cultural barriers to access to care.

Infertility as a Couple’s Problem

It is extremely important to emphasize that infertility is a problem affecting both partners. The causes of difficulties in getting pregnant are more or less evenly distributed: the female factor is responsible for about 35-40% of cases, the male factor also accounts for 35-40%, in about 10-20% of cases the problem lies on both sides (partner factor), and in the remaining 10-20% of cases the cause cannot be clearly determined (idiopathic infertility). Therefore, it is crucial to involve both partners in the diagnostic and therapeutic process from the very beginning.

Types of Infertility: Primary, Secondary and Idiopathic

Infertility is not a uniform condition. There are several types of it, which is important both for understanding the problem and for directing diagnostics and treatment.

Primary infertility (Sterilitas primaria)

Primary infertility is defined as a situation in which a woman has never become pregnant before, despite at least a year of trying to conceive a child with regular intercourse without contraception. This applies to couples who are trying to conceive offspring for the first time. This type of infertility is prevalent in developed countries. Diagnosis for primary infertility can cover a wide range of potential causes, including birth defects, chronic conditions that have been around for a long time, or genetic factors.

Secondary infertility (sterilitas secundaria)

Secondary infertility is diagnosed in couples who have already had a pregnancy before (regardless of its outcome – live birth, stillbirth, miscarriage or ectopic pregnancy), but currently have difficulty getting pregnant again for at least 12 months. Having a child in the past is not a guarantee of fertility in the future, which is important in the context of problems with getting pregnant. It is estimated that this problem may affect up to 15% of couples trying to have another child , and in some groups, e.g. men with varicocele, it may be responsible for up to 80% of cases of secondary infertility.

The causes of secondary infertility can be similar to the primary one, but they are often due to factors that have arisen after a previous pregnancy or over time, which a gynaecologist can assess. These may include changes in the woman’s body after pregnancy or childbirth (e.g. adhesions in the uterus, damage to the fallopian tubes), acquired diseases (e.g. endometriosis, thyroid diseases), complications after abdominal surgery, past infections of the genitourinary system, lifestyle factors (stress, stimulants, weight change), and above all, a natural decrease in fertility related to the age of both partners. In developing countries, secondary infertility is more common, often as a consequence of untreated sexually transmitted diseases. The distinction between primary and secondary infertility is important because in the case of the latter, diagnostics can focus on looking for factors that have changed since the last pregnancy.

Idiopathic infertility (of unexplained origin)

Idiopathic infertility, i.e. infertility of unexplained cause, is diagnosed when standard diagnostic tests in both partners do not show any obvious abnormalities that could explain the difficulty in getting pregnant. This applies to about 10-20% of couples struggling with infertility. The couple may have normal hormonal test results, regular ovulation in the woman, normal semen parameters in the man and no visible anatomical defects of the reproductive organs.

However, the diagnosis of “idiopathic infertility” does not mean that the cause does not exist. Rather, it reflects the limitations of current standard diagnostic methods. The causes can be subtle, complex, or difficult to detect with routine testing. Potential hidden causes include: mild hormonal disorders, cervical mucus abnormalities (e.g. increased cellular immunity), problems with the quality of gametes (eggs or sperm) or early embryo development at the genetic level, latent infections, early stages of endometriosis, immunological factors, abnormal blood supply to the uterus, disorders of fallopian tube peristals, or even lifestyle factors or psychological barriers. Treatment for idiopathic infertility is often empirical and may include methods such as ovulation stimulation, intrauterine insemination (IUI) or in vitro fertilisation (IVF), often using ICSI (intracytoplasmic sperm injection). IVF/ICSI is particularly effective because it bypasses many potential, even undiagnosed, barriers to the natural reproductive process.

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Other classifications

It is also worth mentioning less frequently used terms. Sterilitas refers to the permanent inability to conceive, while infertilitas refers to the inability to carry a pregnancy to term. Relative (temporary) infertility or subfertility (sterilitas relativa/temporaria), on the other hand, is a condition in which there is a reversible cause of fertility problems, giving a chance for cure.

Causes of Infertility in Women: An In-Depth Analysis

The female factor is responsible for about 30-40% of infertility cases. The causes can be diverse and relate to different stages of the reproductive process, from egg production, through its transport, fertilization, to implantation of the embryo in the uterus.

Ovulation Disorders: The Role of PCOS and Other Factors

Ovulation disorders are one of the most common causes of infertility in women, accounting for about 25-30% of cases related to the female factor. Ovulation, i.e. the regular release of a mature egg from the ovary, is a necessary condition for natural conception. The disorders may manifest themselves as infrequent ovulation (oligoovulation) or their complete absence (anovulation). The most common symptom of these disorders is irregular menstrual cycles or amenorrhea.

• Polycystic Ovary Syndrome (PCOS): It is the most common endocrine disorder in women of childbearing age, affecting 5-10% of this population and being the main cause of infertility resulting from lack of ovulation (up to 80% of such cases). PCOS is characterized by a combination of symptoms, and for diagnosis (according to the Rotterdam criteria) at least two of the three features are required:
  1. Infrequent or absent ovulation (manifested by irregular or absent periods).
  2. Excess of androgens (male hormones), found clinically (hirsutism, acne, androgenetic alopecia) or biochemically (increased level of androgens in the blood).
  3. Characteristic image of the ovaries on ultrasound (numerous small antral follicles, the so-called “polycystic”, without a visible dominant follicle). The causes of PCOS are not fully understood, but genetic factors and lifestyle are thought to play a role. A key component of the pathophysiology of PCOS is the common insulin resistance, which leads to elevated insulin levels, which in turn stimulates the ovaries to produce androgens and interferes with ovulation. PCOS is also associated with an increased risk of obesity (especially abdominal obesity), metabolic syndrome, type 2 diabetes, cardiovascular disease, sleep apnea, and mood disorders (depression, anxiety). Treatment of PCOS in the context of infertility focuses on restoring ovulation. The first step, especially in overweight or obese women, is lifestyle modification – a healthy diet (often with a low glycemic index), regular physical activity and weight reduction. Even a small amount of weight loss can restore regular cycles. If lifestyle changes are insufficient, ovulation-inducing drug treatments such as clomiphene citrate or letrozole are used. In patients with insulin resistance, metformin may be helpful.
• Other hormonal causes: In addition to PCOS, ovulation disorders can be caused by:
  • Hyperprolactinemia: Excessive secretion of prolactin by the pituitary gland inhibits the secretion of gonadotropins (FSH, LH) and thus ovulation. It can be caused, m.in, by pituitary adenoma, hypothyroidism, or the use of certain medications.
  • Thyroid dysfunction: Both hypothyroidism and hyperthyroidism can disrupt the menstrual cycle and ovulation. Therefore, TSH and thyroid hormone testing is a standard part of infertility diagnostics.
  • Hypothalamic-Pituitary Dysfunction: Disorders in the secretion of GnRH by the hypothalamus or FSH/LH by the pituitary gland can lead to a lack of ovarian stimulation. The causes may be: excessive stress, intense physical exertion, malnutrition (anorexia, bulimia), low body weight, pituitary or hypothalamus tumors.
  • Adrenal Disorders: Excessive production of androgens by the adrenal glands can also interfere with ovulation.
• Premature Ovarian Lapse (POF/POI): It is the loss of normal ovarian function before the age of 40. Women with POF/POI experience menopausal symptoms (e.g., hot flashes, vaginal dryness) and become infertile due to depletion of ovarian reserve or failure of the ovaries to respond to hormonal stimulation. The causes can be genetic (e.g. Turner syndrome, mutations in the FMR1 gene), autoimmune (attack of the immune system on the ovaries), iatrogenic (after oncological treatment – chemo- or radiotherapy) or idiopathic. The diagnosis is made on the basis of clinical symptoms and the results of hormonal tests (high FSH levels, low estradiol and AMH levels). With POF/POI, the chances of pregnancy from one’s own eggs are very low, and the main fertility treatment option is IVF with donor eggs.

The link to the overall metabolic state of the body is of key importance in ovulation disorders, especially in PCOS. Insulin resistance and obesity often coexist with ovulation problems and can exacerbate them. Therefore, lifestyle modification, including a low glycemic index diet, regular physical activity and weight reduction, is not only a supportive element, but often a basic therapeutic intervention. This approach not only increases the chances of restoring ovulation and a natural pregnancy, but also improves overall health and reduces the long-term risk of metabolic and cardiovascular complications associated with PCOS.

Obstruction of the Fallopian Tubes: Causes and Consequences

The fallopian tubes play a key role in the process of natural fertilization. These are delicate structures that transport the egg from the ovary to the uterus and are the place where the egg meets the sperm and fertilizes it. Obstruction of the fallopian tubes, partial or complete, prevents or hinders this process and is the cause of infertility in about 20-25% of women.

• Causes of obstruction: Fallopian tube obstruction is most often the result of adhesions or scars forming in or around the lumen of the fallopian tubes. The most common causes include:
  • Pelvic inflammatory conditions (PID): Mainly caused by sexually transmitted diseases (STIs), such as infection with Chlamydia trachomatis or gonorrhoeae (Neisseria gonorrhoeae). These infections, often asymptomatic (especially chlamydia), can lead to permanent damage to the delicate structure of the fallopian tubes and the formation of adhesions.
  • Endometriosis: Endometrial tissue outside the uterus can cause inflammation and adhesions within the pelvis, including around the fallopian tubes.
  • Postoperative adhesions: can affect female and male fertility. Any abdominal or pelvic surgery (e.g. removal of the appendix, gynaecological surgeries, caesarean section) carries the risk of adhesions, which may involve the fallopian tubes.
  • Previous ectopic pregnancy: Pregnancy developing in the fallopian tube can lead to damage or the need to remove it.
  • Complications after Miscarriage or Abortion: They can lead to infection and inflammation.
  • Uterine fibroids: Especially those located near the openings of the fallopian tubes to the uterus can block them.
  • Congenital defects of the fallopian tubes: A rare cause.
  • Genital tuberculosis: Rare in developed countries.
  • Intrauterine devices (IUDs): Formerly considered a risk factor for PID, the risks associated with modern cylinders are now low, although some sources still list them.
• Symptoms: Fallopian tube obstruction is often asymptomatic and is only detected during infertility diagnosis. However, sometimes you may experience non-specific symptoms, such as pain in the lower abdomen (especially during menstruation, ovulation or intercourse), painful menstruation (especially with endometriosis) or unusual vaginal discharge (if the cause is an active infection).
• Diagnostics: it is crucial for men with fertility problems. The basic methods of assessing fallopian tube patency are:
  • Hysterosalpingography (HSG): X-ray examination with iodine contrast administration into the uterine cavity and fallopian tubes.
  • Sonohysterosalpingography (Sono-HSG, HyCoSy/HyFoSy): Ultrasound examination with the administration of a special contrast agent (foam or saline) to the uterus and fallopian tubes. It is a less invasive method than HSG, it does not use X-rays.
  • Laparoscopy with Chromotubation: An invasive method, performed under general anesthesia, involving the administration of the dye through the cervix and observation of its outflow from the fallopian tubes to the abdominal cavity using a laparoscope. Considered the “gold standard” for diagnostics, it allows you to assess other pelvic structures and possibly remove adhesions at the same time.
• Treatment: The choice of treatment method depends on the cause, location and degree of obstruction.
  • Pharmacological treatment: Antibiotics in case of active infection.
  • Surgical treatment (laparoscopy): It is possible to remove perifallopian tube adhesions or try to unblock the fallopian tubes (e.g. fimbrioplasty, salpingostomy). The effectiveness of the surgery is limited, especially in the case of extensive damage or obstruction in the distal segment (closer to the ovary). Sometimes it is necessary to remove the affected fallopian tube (salpingectomy), especially in the case of hydrosalpinx, as the fluid contained in it can negatively affect the implantation of the embryo in the uterus.
  • In vitro fertilization (IVF): It is the most effective treatment for irreversible obstruction of the fallopian tubes or when surgical treatment is ineffective or not recommended (e.g. in older women). IVF bypasses the fallopian tubes, allowing the egg to be fertilized in the lab and the embryo to be transferred directly into the uterus.

An important aspect of fallopian tube obstruction is that it often results from causes that can be prevented or that can be effectively treated at an early stage, such as sexually transmitted diseases. Chlamydial infections are particularly insidious, as they are often asymptomatic , leading to silent damage to the fallopian tubes. This highlights the paramount importance of sexual health education, the use of safe sexual practices, and regular screening for STIs, as well as prompt treatment of any infections to protect future fertility.

Although laparoscopic surgery offers the possibility of repairing damaged fallopian tubes , its effectiveness is limited, especially in cases of significant damage to the fallopian tube tissue or obstruction in the distal part. Even after successful patency, the transport function of the fallopian tube may not be fully restored. For this reason, for many women with an important fallopian tube factor, especially after the age of 35, in vitro fertilization is becoming the method of choice. IVF effectively bypasses the problematic anatomy of the fallopian tubes, offering the most direct route to pregnancy.

Endometriosis: the silent enemy of fertility

Endometriosis is a chronic disease characterized by the presence of tissue similar to the lining of the uterus (endometrium) outside the uterine cavity. Outbreaks of endometriosis can be found on the ovaries (forming endometrial cysts), fallopian tubes, peritoneum, pelvis, bladder, intestines, and even in remote locations. This tissue responds to cyclical hormonal changes, which leads to chronic inflammation, pain, scarring and adhesions. Endometriosis is a common cause of infertility – it is estimated that it affects one in five women who come to an infertility clinic.

• Effects on Fertility: Endometriosis can make it difficult to get pregnant in many ways. It is estimated that 30-50% of women with endometriosis have fertility problems. Mechanisms include:
  • Anatomical disorders: Adhesions and scarring can distort the anatomy of the pelvis, leading to obstruction of the fallopian tubes or making it difficult for the egg to be released from the ovary and captured by the fallopian tube.
  • Inflammatory environment: Chronic inflammation in the pelvis, caused by outbreaks of endometriosis, can negatively affect the quality of eggs, sperm function, the fertilization process and the implantation of the embryo in the uterus.
  • Ovulation and Ovarian Function Disorders: Endometriosis can affect the maturation process of eggs (oocytes) and potentially interfere with ovulation. Endometrial cysts can damage healthy ovarian tissue and lower the ovarian reserve.
  • Corpus luteum insufficiency: The disease may be associated with disorders of the luteal phase of the cycle.
• Symptoms: The most common symptoms are painful menstruation (often very severe), chronic pelvic pain, pain during intercourse (dyspareunia), pain when urinating or defecating (especially during menstruation), irregular bleeding, and difficulty getting pregnant. It is important to note that the severity of pain symptoms does not always correlate with the severity of the disease or its impact on fertility. Some women with advanced endometriosis may have minor complaints, while others with mild endometriosis may suffer from severe pain.
• Diagnostics: A suspicion of endometriosis is prompted by an interview and gynecological examination. Imaging tests, such as transvaginal ultrasound or magnetic resonance imaging (MRI), can visualize endometrial cysts on the ovaries or deeply infiltrating foci of the disease. However, laparoscopy remains the gold standard in diagnostics, which allows for direct visualization of endometriosis foci, assessment of their extent and collection of samples for histopathological examination.
• Treatment: Management depends on the severity of symptoms, the severity of the disease, the patient’s age and her procreation plans.
  • Symptomatic: Pain relievers (NSAIDs).
  • Hormonal treatment: Contraceptive pills, progestogens, GnRH analogues. They inhibit the development of endometriosis foci and relieve pain, but at the same time prevent pregnancy, so they are not used in women actively trying to conceive.
  • Surgical treatment (laparoscopy): It is aimed at removing visible foci of endometriosis, endometrial cysts and adhesions. It can relieve pain and potentially improve the chances of a natural pregnancy, especially in milder forms of the disease. However, ovarian surgery (cyst removal) may be associated with the risk of removing healthy ovarian tissue and reducing the ovarian reserve, which is especially important in women planning pregnancy. Therefore, the decision to undergo surgery, especially in the case of small cysts (<3 cm), must be carefully considered.
  • Assisted Reproduction Techniques (ART): Intrauterine insemination (IUI) can be considered for mild forms of endometriosis. In vitro fertilization (IVF) is often the most effective treatment for infertility associated with moderate to severe endometriosis, as well as in cases where other methods have failed. Surgical removal of endometriosis foci before IVF may (but not always) increase the chances of success, but this decision must take into account the potential risk to the ovarian reserve.
• Endometriosis and pregnancy: Although it is possible to get pregnant with endometriosis, especially in mild forms or with treatment, these pregnancies may have a slightly higher risk of complications. Studies suggest an increased risk of miscarriage (especially in the first trimester), ectopic pregnancy, premature birth, preeclampsia, low birth weight of the baby, placenta previa and the need for a caesarean section. Therefore, pregnancy in a woman with endometriosis is often treated as a high-risk pregnancy and requires careful monitoring. However, it is worth noting that some guidelines (e.g. ESHRE) indicate the need for a cautious interpretation of these data due to the quality of the studies. Pregnancy alone does not cure endometriosis, although symptoms of the disease may improve temporarily; After childbirth, the disease often returns.

Endometriosis presents a complex clinical challenge as the disease itself impairs fertility through various mechanisms (distortion of anatomy, inflammation, gamete/implantation impact), and at the same time, some treatments, especially surgical removal of ovarian cysts, may carry the risk of further lowering reproductive potential by reducing the ovarian reserve. This requires a very individualized approach to treatment, careful weighing of the benefits and risks of individual interventions in the context of the patient’s priorities (pain vs fertility) and her age and ovarian reserve.

The relationship between endometriosis and pregnancy complications suggests that even after overcoming difficulties with conception, care for pregnant women with endometriosis should be intensified. Although the absolute risk of complications may not be drastically high , awareness of potential risks allows for appropriate monitoring and early response to possible problems.

Uterine problems: defects, fibroids, polyps

The correct structure and function of the uterus are crucial for successful embryo implantation and maintaining pregnancy. Abnormalities in the uterus, both congenital and acquired, can cause infertility or recurrent miscarriages and are responsible for about 20% of female infertility cases.

• Congenital uterine defects: They arise as a result of disorders in the development of the Müllerian ducts during a woman’s fetal life. The most common of them are:
  • Uterus septus: Inside the uterine cavity there is a septum (connective tissue or muscular) that can divide it partially or completely. It is the most common uterine defect, strongly associated with infertility, recurrent miscarriages and premature births. Treatment consists of hysteroscopic removal of the septum (hysteroscopic metroplasty).
  • Bicornuate uterus (Uterus bicornis): It is characterized by a dimple in the uterine fundus, giving it the shape of a heart or the letter W. Benign forms may not affect fertility, but a deeper dimple increases the risk of miscarriages, premature births, and abnormal fetal position.
  • Unicorned uterus (Uterus unicornis): Only one half of the uterus develops. It is associated with an increased risk of infertility and obstetric complications.
  • Double uterus (Uterus didelphys): Complete duplication of the uterus, often also of the cervix and vagina. It does not always cause infertility, but it can increase the risk of miscarriages and premature births.
  • Arcuate uterus (Uterus arcuatus): A small indentation in the uterine fundus. Currently, it is often considered a variant of the norm, with little clinical significance for fertility, which can lead to infertility affects women and men.
• Acquired Uterine Lesions:
  • Uterine fibroids (leiomyoma): These are benign tumors originating in the myometrium, very common in women of childbearing age. Their effects on fertility depend on location and size. The most important are submucosal fibroids (growing inside the uterine cavity) and large intramural fibroids (>6-8 cm), which can distort the uterine cavity, hinder embryo implantation, block the fallopian tube openings or cause inflammation of the endometrium. Subserous fibroids (growing outside the uterus) usually do not affect fertility unless they are very large. Fibroids can cause heavy and painful menstruation. Treatment consists of surgical removal (myomectomy), most often hysteroscopic (for submucosal) or laparoscopic/laparotomy (for intramural and subserous).
  • Endometrial polyps: Benign growths of the endometrium. They can hinder embryo implantation. They are detected by ultrasound, sono-HSG or hysteroscopy and removed during surgical hysteroscopy, which may be necessary when the doctor considers it indicated.
  • Intrauterine adhesions (synechiae uteri, Asherman’s syndrome): Scarring adhesions inside the uterine cavity, most often arising as a complication after curettage procedures (e.g. after miscarriage, childbirth), uterine surgery or endometrialitis. They can lead to a decrease in the volume of the uterine cavity, menstrual disorders (scanty menstruation, amenorrhea) and problems with embryo implantation. They are diagnosed and treated by hysteroscopy (hysteroscopic release of adhesions).
  • Adenomyosis: Presence of endometrial tissue within the myometrium. It can cause pain, heavy bleeding, and potentially affect fertility.
• Diagnostics: To assess the uterus, ultrasound (especially three-dimensional – 3D ultrasound), hysterosalpingography (HSG) or sonohysterosalpingography (HyCoSy), which are recommended by the gynaecologist in the diagnosis of infertility, are used. , and the gold standard in the assessment of the uterine cavity is hysteroscopy. Laparoscopy allows you to assess the external shape of the uterus.

The influence of uterine factors on fertility is varied. Not every detected abnormality requires intervention. Submucosal fibroids, large intramural fibroids that distort the uterine cavity and the uterine septum are generally considered to be significant obstacles to pregnancy and often qualify for surgical treatment, usually hysteroscopic. Other changes, such as small intramural fibroids or arcuate uterus, may have little effect on fertility and do not always require treatment. Precise diagnosis using appropriate imaging techniques (ultrasound, hysteroscopy ) is crucial to make the right therapeutic decision and avoid unnecessary procedures.

Immune Infertility in Women

The immune system plays a complex role in the reproductive process. On the one hand, it protects the body against infections, on the other hand, it must tolerate the presence of the partner’s “foreign” antigen sperm and the developing embryo. Disorders in the functioning of the immune system can lead to immune infertility, which affects about 6-12% of couples with infertility problems. It can take the form of autoimmunity (the immune system attacks its own reproductive tissues) or alloimmunisation (an immune reaction against the partner’s cells or embryo).

• Autoimmune factors:
  • Antiovarian Antibodies (AOA): Directed against ovarian cells, they can damage oocytes, interfere with hormone production, lead to premature ovarian failure or reduce the quality of eggs.
  • Antiphospholipid Syndrome (APS): The presence of antiphospholipid antibodies (anticardiolipin antibodies, lupus anticoagulant, antibodies against beta2-glycoprotein I) is associated with an increased risk of thrombosis, recurrent miscarriages and implantation failures, probably due to disorders in the uteroplacental circulation.
  • Antithyroid Antibodies (anti-TPO, anti-TG): A marker of autoimmune thyroid diseases (e.g., Hashimoto’s), which in themselves can affect fertility through ovulation disorders and an increased risk of miscarriages.
  • Antinuclear Antibodies (ANA): They can indicate a systemic autoimmune disease and potentially negatively affect the endometrial environment, causing inflammation.
• Alloimmune factors:
  • Antisperm Antibodies (ASA) in Women: Antibodies produced by the woman’s immune system present in the cervical mucus or genital tract can attack the partner’s sperm, impairing their motility, ability to penetrate cervical mucus, capacitation (the process of preparing for fertilization) or fertilization itself.
  • Problems with Immune Tolerance of the Embryo: Pregnancy requires the mother’s immune system to tolerate antigens from the father present in the embryo. Disorders of this tolerance can lead to implantation failures or miscarriages. This process involves complex interactions between immune cells (T lymphocytes, NK cells – Natural Killer cells), cytokines (Th1/Th2 balance) and HLA molecules on the surface of the embryo and maternal cells. Abnormal activity of natural killer cells in the uterus (uNK), unfavorable combinations of the mother’s KIR and HLA-C genes of the embryo (from the father), disturbed cytokine balance or lack of so-called blocking antibodies (Allo-MLR) can contribute to problems with maintaining pregnancy.
• When to suspect immune infertility: Diagnostics in this direction is considered especially in cases of idiopathic infertility, recurrent embryo implantation failures in IVF procedures, recurrent miscarriages, as well as in patients with coexisting autoimmune diseases (e.g. Hashimoto’s, lupus, celiac disease) or frequent inflammation of the genital organs.
• Diagnostics: It requires specialized laboratory tests, often from blood. The test panel may include: determination of AOA antibodies, panel of tests for APS (anti-cardiolipin, anti-β2GP1, lupus anticoagulant), antithyroid antibodies, ANA, ASA (in serum, cervical mucus), assessment of lymphocyte subpopulation (including NK cells and their cytotoxic activity), assessment of the cytokine profile (Th1/Th2), KIR and HLA-C gene typing in both partners, blocking antibody test (Allo-MLR).
• Treatment: It is highly specialized, often empirical and controversial, because not all methods have proven effectiveness in clinical trials. It may include treatment of the underlying disease (e.g., autoimmune), use of immunosuppressive drugs (e.g., corticosteroids, tacrolimus), anticoagulants (heparin, acetylsalicylic acid in APS), intravenous infusions of immunoglobulins (IVIg) or intralipids, as well as assisted reproductive techniques (IUI, IVF/ICSI) that can bypass some immune barriers (e.g., ASA in the cervical mucus). It requires close cooperation with a doctor specializing in reproductive immunology.

The field of reproductive immunology is complex and dynamically developing. Many diagnostic tests and proposed therapies are not yet established in evidence-based medicine, leading to differences in clinical approaches between specialists. Patients should be aware that immunotherapy is often experimental and requires careful consideration of potential benefits and risks.

The presence of autoimmune markers, such as antithyroid antibodies, may be important in the diagnosis of infertility in women – causes. whether antinuclear antibodies (ANA), even in the absence of a full-blown autoimmune disease, can be a warning signal. Such findings in a woman struggling with infertility or recurrent pregnancy loss may justify further, in-depth immunological diagnostics or affect treatment planning, including ART protocols.

The Impact of Age on Female Fertility

Age is one of the most important, if not the most important, factor determining a woman’s fertility, especially after several months of trying. Unlike men, who produce sperm for most of their adult lives, women are born with a finite number of eggs, the quantity and quality of which decreases as the years go by.

• Peak Fertility and Decline: A woman reaches peak fertility between the ages of 20 and 25 or more broadly, in the third decade of life (20-30 years). After the age of 30, fertility begins to gradually decrease, and this decline becomes more pronounced after the age of 35. After the age of 40, the chances of natural conception decrease drastically, and after the age of 45 they are already minimal. The estimated chance of getting pregnant in one cycle drops from about 20-25% in young women to about 20% by age 30, 12% by age 35 and only 5-7% by age 40. A woman’s overall fertility at the age of 35 may be about 60% of her peak value, and at the age of 40 it is only 10-15%.
• Mechanisms of fertility decline: Age-related decline in fertility is due to two main processes:
  1. Ovarian reserve (number of eggs) decreased: A woman is born with about 1-2 million oocytes, and during puberty there are 300-500 thousand of them. This number is constantly decreasing with each menstrual cycle (not only through ovulation, but mainly through the process of atresia – the natural disappearance of follicles). At the age of 30, a woman has an average of 100-150 thousand oocytes, at the age of 35 about 80 thousand, and at the age of 40 only 10-25 thousand. The ovarian reserve can be assessed by hormonal tests (AMH, FSH, estradiol levels at the beginning of the cycle) and ultrasound (number of antral follicles – AFC). Low AMH levels, high FSH or low AFC counts indicate a reduced ovarian reserve.
  2. Deterioration of egg quality: With age, the risk of errors during meiotic division in maturing oocytes increases, leading to an increased incidence of aneuploidy (abnormal chromosome count) in eggs. Aneuploid embryos have much less chance of proper implantation and development. This is the main reason for lower fertilization rates, higher rates of miscarriages, and an increased risk of having a child with genetic defects such as Down syndrome (trisomy 21), Edwards syndrome (trisomy 18), and Patau syndrome (trisomy 13) in older mothers. The risk of Down syndrome increases from about 1 in 1250 in a 25-year-old woman to 1 in 400 in a 35-year-old.
• Clinical implications: A woman’s age is a key prognostic factor in the treatment of infertility. In older women, it is necessary to take diagnostic and therapeutic measures faster. More often, they require the use of assisted reproductive techniques (ART), such as IVF. The effectiveness of ART also decreases with age. In older patients, preimplantation embryo diagnosis (PGT-A) is more often considered for the selection of eugenic embryos. In addition, older women are more likely to suffer from other conditions that can affect fertility, such as fibroids or endometriosis.
• Social Context: The trend in developed countries to postpone motherhood is one of the main factors contributing to the increase in the incidence of fertility problems.

The key issue is to distinguish between the quantity and quality of eggs. Ovarian reserve tests (AMH, AFC, FSH ) provide information mainly about the remaining follicle count and the predicted response to hormonal stimulation in IVF. However, they do not directly measure the quality of oocytes, which is closely related to age. A woman may have a formally “normal” ovarian reserve for her age, but still experience difficulty getting pregnant or keeping it pregnant due to reduced egg quality (high rates of aneuploidy). Therefore, age remains one of the strongest independent predictors of the success of infertility treatments, even with the use of ART, and is the main reason why PGT-A is considered in older patients.

The contemporary social trend of postponing the decision to become a parent is in direct contradiction to the biological reality of a decline in female fertility after the age of 35. This conflict is a significant driver of the increasing incidence of age-related infertility and the increased demand for assisted reproductive technologies. This highlights the importance of fertility education and conscious family planning.

Causes of Infertility in Men: What Does the Research Say?

The male factor is as common a cause of infertility as the female factor, being responsible for about 35-40% of cases. If you take into account situations in which male problems coexist with female problems, the male factor plays a role in more than 60% of couples struggling with infertility. The causes of male infertility are diverse and can relate to sperm production, function, transport or ejaculation problems.

Semen Quality: Sperm Count, Motility and Morphology

The basic test in the assessment of male fertility is semen analysis, called a seminogram. This test evaluates a number of physicochemical and microscopic parameters of the ejaculate.

• WHO Key Parameters and Standards 2021: The World Health Organization regularly publishes reference values for semen parameters. The current standards from 2021 are presented in the table below. It should be remembered that these are the lower limits of the norm, and values above these thresholds do not guarantee fertility, just as results below normal do not automatically mean infertility. The interpretation of the result should always be made by the doctor in the context of the entire clinical situation of the couple. Reference values for semen parameters according to WHO 2021

Parameter	Lower limit of normal (≥)	Unit	Origin
Ejaculate volume	1,4	Ml
ph	7,2	–
Sperm concentration	16	million/ml
Total sperm count	39	million in ejaculate
Total mobility	42	%
Progressive mobility	30	%
Vitality	54	% Alive
Morphology (normal forms)	4	%
Leukocytes	< 1	million/ml	(WHO Standard)
Liquefaction time	< 60	Minutes

• Irregularities in the Seminogram: Deviations from the norms in individual parameters have their names:
  • Oligozoospermia: Too low sperm concentration.
  • Asthenozoospermia: Abnormal (too low) sperm motility.
  • Teratozoospermia: Abnormal structure (morphology) of sperm.
  • Oligoasthenoteratozoospermia (OAT): A combination of the above disorders.
  • Azoospermia: Complete absence of sperm in the ejaculate. It requires further diagnosis to distinguish between obstructive azoospermia (blockage of the exit tract) and non-obstructive azoospermia (production disorders).
  • Cryptozoospermia: Very few sperm cells are found only after centrifugation of the semen sample.
  • Leukocytospermia: An increased number of white blood cells (leukocytes) in the semen, which may indicate inflammation.
• Advanced semen analysis: In some cases, especially in the case of idiopathic infertility, recurrent miscarriages or ART failures, additional, more advanced tests are performed to assess sperm function:
  • Sperm DNA fragmentation test (e.g. halosperm, SCSA, TUNEL): It assesses the degree of damage to the genetic material in sperm, which is important in the diagnosis of problems on the part of a man. High DNA fragmentation can negatively affect embryo development and chances of pregnancy.
  • Sperm Binding Test with Hyaluronan (HBA): It assesses the maturity of sperm and their ability to bind to hyaluronic acid, which is important in the fertilization process.
  • Assessment of Oxidative Stress (e.g. Mioxsys test): It measures the level of reactive oxygen species in semen, the excess of which can damage sperm.
  • MSOME (Motile Sperm Organelle Morphology Examination): Assessment of sperm morphology under very high magnification (>6000x), used for sperm selection in the IMSI procedure.

The observation that the WHO standards for semen parameters have decreased over the past decades is important. This suggests a potential population-wide trend of decline in male sperm quality, which may be related to environmental factors and the lifestyle of modern society. That is why it is so important to use current reference values (WHO 2021 ) to interpret the results of the seminogram to avoid misclassification.

A basic semen analysis provides key information about sperm count, motility, and structure, but it is not a complete picture of male reproductive potential. Even with results within normal range, there may be underlying problems at the level of sperm function or genetic integrity. Advanced tests, such as DNA fragmentation testing, allow for a deeper assessment and can explain the causes of procreative failures in cases where the underlying seminogram does not indicate obvious problems.

Hormonal Disorders: Hypogonadism and Others

The proper functioning of the male reproductive system is tightly controlled by the endocrine system, especially the hypothalamic-pituitary-gonadal (HPG) axis. The hypothalamus secretes gonadotropin-releasing hormone (GnRH), which stimulates the pituitary gland to produce luteinizing hormone (LH) and follicle-stimulating hormone (FSH). LH stimulates the Leydig cells in the testes to produce testosterone, the main male sex hormone. FSH, along with testosterone, is essential for the proper course of spermatogenesis (sperm production) in the seminiferous tubules of the testicles. Disorders at any level of this axis can lead to infertility.

• Male hypogonadism: It is a condition characterized by insufficient testicular function, leading to decreased testosterone production and/or impaired sperm production. There are several types:
  • Primary (hypergonadotropic) hypogonadism: The problem lies in the testicles themselves, which do not respond properly to hormonal stimulation from the pituitary gland. FSH and LH levels in the blood are elevated and testosterone levels are low. The causes are, m.in, Klinefelter syndrome, testicular damage (injury, torsion, inflammation, e.g. after mumps), cryptorchidism, oncological treatment (chemotherapy, radiotherapy), some autoimmune diseases. In primary hypogonadism, restoring sperm production is usually impossible, and infertility treatment requires ART techniques.
  • Secondary (hypogonadotropic) hypogonadism: The problem lies in the hypothalamus or pituitary gland, which do not produce enough GnRH, LH, or FSH. The testicles are potentially capable of producing testosterone and sperm, but they lack adequate stimulation. FSH, LH, and testosterone levels are low or at the lower end of normal. The causes are, m.in, pituitary or hypothalamus tumors, head injuries, radiation therapy of the head area, Kallmann syndrome (congenital GnRH deficiency with olfactory disorders), severe systemic diseases, malnutrition, excessive physical exertion, chronic stress, obesity, certain medications. In secondary hypogonadism, it is possible to pharmacologically stimulate sperm production with gonadotropins (hCG, hMG, recombinant FSH).
  • Peripheral hypogonadism: It results from tissue insensitivity to androgens (e.g. in androgen insensitivity syndrome).
  • Functional hypogonadism: Caused by other diseases or conditions (e.g., obesity, severe chronic diseases) that secondarily impair the function of the HPG axis.
• Symptoms of hypogonadism: They can be diverse and depend on the age of onset and severity of testosterone deficiency. In adult men, the most common symptoms are: decreased libido, erectile dysfunction, fatigue, decrease in muscle mass and strength, fat gain (especially abdominal fat), mood changes (depression, irritability), gynecomastia (enlarged mammary glands), decreased male pattern hair, small, soft testicles and infertility (usually associated with a reduced sperm count).
• Diagnostics: It includes medical history, physical examination and hormonal blood tests (determination of total testosterone levels – preferably in the morning, FSH, LH, prolactin, estradiol, DHEA-S, thyroid hormones). Depending on the suspected cause, additional tests may be ordered, such as pituitary imaging (MRI) or genetic testing.
• Treatment: Treatment of symptoms of hypogonadism involves Testosterone Replacement Therapy (TRT) in the form of injections, gels, or patches. However, TRT inhibits the testicles’ own sperm production and is contraindicated in men trying to conceive. Men wishing to preserve fertility, especially those with secondary hypogonadism, require spermatogenesis-stimulating treatment with gonadotropin injections (hCG and/or FSH). This treatment is long-term and requires monitoring. In the case of primary hypogonadism, fertility treatment is based on ART techniques using possibly found sperm (e.g. after TESE) or donor sperm. Lifestyle modifications such as weight reduction and stress management also play an important role.
• Other hormonal disorders: Elevated levels of prolactin (hyperprolactinemia) can inhibit the production of gonadotropins and testosterone. Thyroid dysfunction (hypothyroidism or hyperthyroidism) can also negatively affect fertility.

An extremely important aspect, often underestimated by patients, is the negative impact of testosterone replacement therapy (TRT) and the use of anabolic-androgenic steroids (AAS) on fertility. Exogenous administration of testosterone or its derivatives inhibits the natural production of gonadotropins (LH and FSH) by the pituitary gland on a negative feedback basis. This results in inhibition of testicular stimulation and, consequently, stopping or significantly reducing spermatogenesis, leading to infertility. Men who use TRT (with a doctor’s prescription or illegally as anabolics ) and at the same time trying to conceive must absolutely stop this therapy. Restoring sperm production may require time and often pharmacological support with gonadotropins (hCG, FSH). This is key information for couples planning to have children.

Genetic factors: Klinefelter syndrome, microdeletions

Genetic factors play a significant role in male infertility, causing problems in about 15% of infertile men. They can relate to abnormalities in the number or structure of chromosomes, or mutations in individual genes, affecting the development of testicles, hormone production or the process of spermatogenesis itself. The suspicion of a genetic background arises especially in cases of severe oligozoospermia (significantly reduced sperm count) or azoospermia (complete absence of sperm in semen).

• Chromosomal abnormalities:
  • Klinefelter syndrome (karyotype 47,XXY): It is the most common chromosomal cause of male infertility. Men with this syndrome have an extra X chromosome. Characteristic features include small, hard testicles, reduced testosterone levels, often gynecomastia, tall stature, sometimes learning difficulties. Azoospermia or very severe oligozoospermia usually occurs due to progressive fibrosis of the seminiferous tubules, which can be a problem on the part of the man. The risk of Klinefelter syndrome increases with the age of the mother. Despite severe spermatogenesis disorders, in some men with Klinefelter syndrome (especially younger men or with 46,XY/47,XXY mosaicism) it is possible to find foci of sperm production in the testicles by means of surgical biopsy (TESE or micro-TESE) and use them for ICSI fertilization.
  • Other sex chromosome aneuploidies: e.g. 47,XYY syndrome, mosaics.
  • Chromosomal Translocations (Reciprocal and Robertsonian): Exchange of fragments between chromosomes. If the translocation is balanced, the carrier is usually healthy, but may produce gametes with unbalanced genetic material, leading to infertility, implantation failures, or recurrent miscarriages. In such cases, genetic counseling and consideration of embryo preimplantation diagnosis (PGT-SR) are recommended.
• Y-chromosome microdeletions (AZF region): The Y chromosome contains genes crucial for male development and spermatogenesis, located, m.in, in the AZF (Azoospermia Factor) region of the long arm (Yq). Microdeletions, or the loss of small DNA fragments in this region, are a common cause of severe oligozoospermia or non-obstructive azoospermia. They occur in 5-25% of men with these problems. There are three subregions: AZFa, AZFb and AZFc. The AZF microdeletion test is recommended in men with sperm concentrations below 5-10 million/ml. The result has prognostic significance for the possibility of finding sperm during a testicular biopsy:
  • Complete deletions of AZFa or AZFb are associated with a lack of spermatogenesis and no chance of finding sperm.
  • AZFc deletions (the most common) often allow to find foci of spermatogenesis and obtain spermatozoa by TESE to ICSI. AZF microdeletions are inherited from father to son.
• Mutations of single genes:
  • CFTR gene mutations: This gene is responsible for the production of a protein that regulates the transport of chloride ions. Mutations in this gene are the cause of cystic fibrosis. In men, specific mutations in the CFTR gene, even if they do not cause full-blown cystic fibrosis, are the main cause of congenital bilateral vas deferens absence (CBAVD), resulting in obstructive azoospermia. CFTR mutation testing is recommended in men with azoospermia or severe oligozoospermia, especially before ART, to diagnose infertility. If the mutation is detected, it is also necessary to test the partner for carrier status to assess the risk of giving birth to a child with cystic fibrosis. In men with CBAVD, sperm can be obtained surgically (PESA/TESE) by ICSI, which is important in the diagnosis and treatment of infertility.
  • Mutations in the androgen receptor (AR) gene : They cause androgen insensitivity syndrome (AIS), leading to disorders of sexual development and infertility.
  • Other genes: Mutations in genes such as KAL1 (associated with Kallmann syndrome), INSL3, RXFP2 (associated with cryptorchidism) can also contribute to infertility.
• Mitochondrial DNA (mtDNA) mutations: Mitochondria provide energy for sperm movement. Mutations in mtDNA can lead to decreased ATP production and impaired sperm motility (asthenozoospermia).
• Genetic Diagnostics: It includes karyotype analysis (analysis of chromosomes from peripheral blood), analysis of microdeletions of the AZF region of the Y chromosome, which may reveal abnormalities in the structure of sperm. and testing for mutations in the CFTR gene. A consultation with a geneticist is recommended.

Genetic testing plays a key role in the diagnosis of severe male infertility. Their results are not only diagnostic, but above all prognostic. They allow to predict the chances of success of surgical sperm recovery (e.g. no chance in the case of AZFa/b deletion, good chances in the case of AZFc deletion) and assess the risk of passing the genetic defect to the offspring. This information is necessary for informed decision-making regarding further treatment, including the choice of ART method (e.g. the need for ICSI using sperm from biopsies and possible preimplantation diagnosis (PGT) can help diagnose infertility, which the gynaecologist may include in the treatment plan.

Even in the case of serious genetic disorders, such as Klinefelter syndrome or AZFc deletions, which used to mean permanent infertility, modern reproductive medicine offers a chance for biological fatherhood. By combining advanced surgical sperm retrieval (TESE/micro-TESE ) techniques with in vitro fertilization using ICSI , many men with these conditions can become fathers. This shows how assisted reproductive technologies can overcome significant biological barriers.

Obstruction of the semen exit tracts

In this type of infertility, the testicles produce sperm normally, but they cannot be expelled with the ejaculate due to a blockage in some section of the semen ducts (epididymis, vas deferens, ejaculatory duct). This condition is called obstructive azoospermia (OA), which is one of the ovulation disorders in men.

• Causes:
  • Congenital bilateral absence of the vas deferens (CBAVD): A malformation often associated with mutations in the CFTR gene.
  • Infections and Inflammation: can affect fertility and are often examined by gynecologists. A history of epididymitis, prostatitis or sexually transmitted infections (gonorrhea, chlamydia) can lead to scarring and narrowing in the ducts.
  • Surgical operations: Damage to the vas deferens can occur during inguinal hernia surgery, surgery within the scrotum or pelvis. Vasectomy (deliberate cutting of the vas deferens as a method of contraception) also leads to obstructive azoospermia.
  • Injuries: Injuries to the perineal or pelvic area.
  • Obstruction of the ejaculatory ducts: Caused, for example, by cysts in the prostate area.
• Diagnostics: Obstructive azoospermia typically shows a lack of sperm in the semen with normal testicular size and normal (or slightly elevated) levels of FSH and LH hormones. The volume of the ejaculate may be reduced and its pH low (acidic), especially with obstruction of the ejaculatory ducts or lack of seminal vesicles. Diagnosis includes a physical examination (palpation of the vas deferens), transrectal ultrasonography (TRUS) to evaluate the seminal vesicles and ejaculatory ducts, genetic testing (especially tests for CFTR mutations), and sometimes a radiological examination called vasography.
• Treatment: In some cases, it is possible to surgically restore the patency of the semen ducts:
  • Vasovasostomy: Reconnection of the cut ends of the vas deferens (e.g. after vasectomy).
  • Vazoepididymostoma: Connection of the vas deferens directly to the epididymis in the case of obstruction within the epididymis.
  • Transurethral resection of the ejaculatory ducts (TURED): Removal of an obstruction in the ejaculatory ducts with an endoscope inserted through the urethra. The success rate of reconstructive surgery, especially vasectomy reversal, can be high, but it depends on the time that has elapsed since the original surgery or injury, and the surgeon’s experience. An alternative, and often the method of choice, is surgical sperm collection directly from the epididymis (PESA – percutaneous aspiration, MESA – microsurgical aspiration) or testicle (TESA – aspiration, TESE – open biopsy, micro-TESE – microsurgical biopsy). The collected sperm are then used for in vitro fertilization using the ICSI method.

Obstructive azoospermia (OA) generally has a better prognosis in terms of the possibility of producing biological offspring than non-obstructive azoospermia (NOA), because sperm production in the testes is preserved. This means that surgical methods of sperm retrieval (PESA, TESA, TESE ) have a very high efficiency in obtaining the gametes needed for the ICSI procedure. In the case of NOA, where the problem lies in the sperm production itself, the chances of finding sperm during a testicular biopsy are lower. This distinction is critical for counseling and treatment planning in men with azoospermia.

Varicocele

Varicoceles are a widening of the flagellar plexus veins (veins draining blood from the testicles) within the scrotum. It is a relatively common condition, occurring in about 15% of the general male population, but much more often diagnosed in men with fertility problems (up to 40%). They usually occur on the left side, which is due to the anatomy of the venous system, and the gynaecologist may order further tests.

• Effects on Fertility: It is believed that varicoceles can negatively affect fertility through several mechanisms, mainly related to an increase in temperature in the scrotum. Normal spermatogenesis requires a temperature several degrees lower than the temperature inside the body. Blood stasis in dilated veins leads to overheating of the testicles, which can interfere with sperm production and maturation, leading to a decrease in sperm count, motility and deterioration of morphology. Varicose veins can also cause oxidative stress in the testicles and lead to progressive damage to the nuclear tissue and a decrease in testicular volume (atrophy). They are associated with both primary infertility (about 35% of cases) and secondary infertility (up to 80% of cases).
• Symptoms: In most cases, varicoceles are asymptomatic. If symptoms do occur, they may include a feeling of heaviness or a dull pain in the scrotum, worsening when standing, during physical exertion, or at the end of the day. Sometimes dilated venous vessels, described as a “worm sac”, are visible or felt. In some men, a reduction in the testicle on the varicose vein side is observed.
• Diagnostics: Diagnosis is based on a physical examination of the scrotum in a standing and lying position, with evaluation during the Valsalva test (abdominal muscle tension). Confirmation and assessment of the stage of advancement is an ultrasound examination of the scrotum with Doppler assessment of blood flow. Varicose veins are classified in grades I-III depending on their size and palpability.
• Treatment: The only effective treatment is surgical intervention aimed at closing or ligating dilated veins (varicococytomy). The available methods are:
  • Classical Surgery (e.g. Palomo method): With an incision in the groin area.
  • Laparoscopy: Minimally invasive transperitoneal method.
  • Microsurgery: Surgery with the use of a microscope, performed from a small incision in the groin or under the groin. It is currently considered the method of choice due to the highest precision, the lowest risk of recurrence and complications (e.g. damage to the testicular artery, hydrocele of the testicle).
  • Transvascular embolization: Interventional radiology procedure involving the closure of the testicular vein from the inside with special materials (spirals, adhesives), performed under local anesthesia.
  Indications for surgical treatment are under discussion. They are usually recommended in men with symptomatic varicose veins, large varicose veins (II or III degree) and at the same time abnormal semen parameters and diagnosed infertility (after excluding other causes), as well as in adolescents with testicular growth inhibition on the varicose vein side. Treatment may lead to improved sperm parameters and potentially increase the chances of a natural pregnancy or improve ART scores. However, the benefits of treatment, especially in small, asymptomatic varicose veins (grade I) or in men with normal sperm parameters, are uncertain and surgery in such cases is usually not recommended.

Although varicoceles are a common find in infertile men and there is a reliable mechanism for their negative effects on fertility (testicular overheating, oxidative stress), the decision on surgical treatment should be made on a case-by-case basis. The benefits of varico-selectomy in terms of improving fertility are not conclusively proven in all cases, especially with minor lesions or when the couple is still eligible for ART.

Environmental Factors and Lifestyle

Accumulating evidence points to a significant impact of environmental and lifestyle factors on male fertility. Many of these factors are modifiable, which creates the opportunity to improve reproductive potential by changing habits.

• Age: is an important factor in the diagnosis and treatment of infertility. As in women, male fertility also decreases with age, although this decline is slower and begins later. After the age of 34-40, there may be a gradual deterioration of semen parameters (number, motility). Older age of the father is also associated with a slightly higher risk of certain de novo genetic mutations in the offspring.
• Body Weight (Obesity and Underweight): Excessive body weight (obesity, BMI > 30) has a proven negative effect on male fertility. Obesity leads to hormonal disorders (decreased testosterone levels, increased estrogen levels due to aromatization in adipose tissue), deterioration of semen parameters (lower concentration, motility, morphology), increased sperm DNA fragmentation, increased oxidative stress and inflammation in the body, and more frequent erection problems. Weight reduction through diet and exercise can improve hormonal parameters and sperm quality. Also being underweight (BMI < 18.5) can negatively affect fertility.
• Diet: Diet has a significant impact on sperm quality. A diet rich in processed foods, simple sugars, saturated and trans fats (present in fast food, sweets, hard margarines) is harmful. Fertility is positively affected by a diet rich in antioxidants (vitamin C, E, lycopene), zinc, selenium, folic acid, omega-3 fatty acids. Fresh vegetables and fruits, whole grains, lean protein (poultry, fish, legumes), nuts and seeds are recommended. The Mediterranean diet is often recommended for men with fertility problems. It is also important to properly hydrate the body.
• Smoking: Smoking cigarettes is one of the main modifiable risk factors for male infertility. Toxic substances contained in tobacco smoke (nicotine, cadmium, polycyclic aromatic hydrocarbons) damage sperm DNA, reduce sperm count (by 23% on average in smokers), motility and morphology, disrupt hormonal balance and increase oxidative stress. Both active and passive smoking have a negative impact. Interestingly, a mother’s smoking during pregnancy can result in a lower sperm count in her son in adulthood.
• Alcohol: Excessive alcohol consumption negatively affects male fertility. It can lower testosterone levels, deteriorate sperm quality (sperm count, motility, morphology), reduce libido and cause erectile dysfunction. Alcohol also hinders the absorption of minerals important for fertility, such as zinc. Even occasional drinking of large amounts of alcohol can be harmful. Limiting alcohol consumption is recommended for couples trying to conceive and can improve outcomes for treatment, including IVF.
• Drugs and Medicines: The use of recreational drugs (e.g., it can lead to infertility affects both men and women. marijuana) and anabolic-androgenic steroids (AAS) has a negative impact on sperm production and hormonal balance. Also, some prescription drugs can impair fertility, m.in. drugs used in cancer chemotherapy, some drugs for hypertension, antidepressants, cimetidine, spironolactone, nitrofurantoin. It is important to tell your doctor about all the medications and supplements you are taking.
• Increased testicular temperature: The testicles are located in the scrotum outside the abdominal cavity to maintain a temperature a few degrees lower than the temperature of the rest of the body, which is optimal for spermatogenesis. Overheating of the testicles can interfere with sperm production. Risk factors include, m.in, frequent use of hot baths and saunas, wearing tight, breathable underwear, prolonged sitting (e.g. in professional drivers), holding a laptop on your lap, working in high temperatures, and may affect problems with getting pregnant. and varicocele.
• Stress: Chronic psychological stress can negatively affect fertility through hormonal disorders (elevated cortisol inhibits testosterone production) and decreased libido and problems with sexual function. Stress from work or unemployment can also impair sperm quality.
• Environmental toxins: Exposure to various types of environmental pollutants and chemicals is increasingly indicated as a risk factor for male infertility. The following can be particularly harmful:
  • Pesticides: When used in agriculture, they can act as endocrine disruptors (EDCs) and cause oxidative stress.
  • Heavy Metals: Lead, mercury, cadmium can accumulate in the body and disrupt sperm production and hormonal functions. Exposure can come from contaminated water, food (e.g. fish), air or the workplace.
  • Phthalates: Added to plastics (PVC), cosmetics, packaging; they can act as EDCs.
  • Bisphenol A (BPA): Component of some plastics and epoxy resins (e.g. canned); it can disrupt the hormonal balance and damage sperm DNA.
  • Dioxins: By-products of industrial processes, present in food of animal origin.
  • Organic solvents: Occupational exposure.
  • Air pollution (smog): It can affect sperm parameters. Exposure to toxins can occur through inhalation, ingestion of contaminated food and water, or skin contact. The period of fetal development is particularly sensitive.
• Infections: Sexually transmitted diseases (chlamydia, gonorrhea, mycoplasma, ureaplasma, herpes virus HSV) can lead to inflammation of the epididymis, prostate, seminal vesicles, and consequently to sperm damage, production of antisperm antibodies or obstruction of the exit ducts. Also, having mumps in childhood or adolescence with a complication in the form of orchitis can permanently damage the testicular tissue. Prostatitis can affect the composition of the seminal fluid and the quality of sperm.
• Physical activity: Regular, moderate physical activity is beneficial for overall health and fertility. It helps to maintain a healthy body weight, reduce stress and improve circulation, which is important in the context of infertility diagnosis and treatment. However, too intense, exhausting exercise can have a negative impact on hormone levels and sperm production.
• Frequency of sexual activity: Regular intercourse (e.g. every 2-3 days) helps to maintain optimal sperm quality. Too long sexual abstinence (more than 5-7 days) can lead to the accumulation of older sperm with poorer motility and a greater degree of DNA fragmentation.