Infertility may arise due to problems in the female, male or both. For a couple to be able to conceive within a normal menstrual cycle, an egg from either the right or left ovary must start developing from the start of the menstruation, continue its development for approximately 14 days, get released from the ovary by ovulation, travel through the Fallopian tube towards the uterus, get fertilized by a sperm, start cell division, reach the uterus, and start implanting within the endometrial layer of the uterus on around the 5th or 6th day of fertilization. A problem in either one or more of these steps may result in infertility.
Infertility is the inability to conceive following 12 months of unprotected regular sexual intercourse. Because fertility in women is known to decrease with advancing age, the waiting time until fertility testing is 6 months in women older than 35 years of age. Infertility is a fairly common condition and is encountered in up to 15% of couples in the reproductive age group. Certain tests should be carried out in couples failing to conceive within a given time period. Fertility testing may reveal health problems in either one or both of the partners, however; it is not uncommon to find normal test results, leading to the diagnosis of unexplained infertility.
Damaged Fallopian tubes and pelvic adhesions
Uterine fibroids
Uterine anomalies
Autoimmune diseases
Unexplained Infertility
Genetic Reasons
Ovulatory problems: Women ovulating with a decreased frequency or not having ovulation at all can suffer from infertility. Conditions including hyperprolactinemia, hyperthyroidism, polycystic ovarian disease, can lead to infertility through the absence of ovulation.
Decreased egg quality or egg count :
The most important factor affecting fertility in women is age. Unlike men who have continuous sperm production throughout their reproductive years, women are born with only a limited amount of eggs, the number and quality of which decrease progressively with advancing age. Some women are born with a lower than normal number of eggs, while others may have a hastened depletion of their egg reserve. Other factors that may contribute to premature depletion of the ovarian reserve are cigarette smoking, radiation therapy, ovarian surgery, chemotherapy and autoimmune diseases. Cell division problems arise in older eggs, decreasing the possibility of achieving embryos with a normal chromosomal number and therefore healthy pregnancies.
Damaged Fallopian tubes and pelvic adhesions :
Damaged tubes and adhesions between pelvic organs may prevent the transport of sperm and egg within the tubes. The most common underlying reason for damaged tubes are past intrapelvic infections caused by some bacteria species as Chlamydia or Neisseria. Other conditions related with damaged Fallopian tubes and pelvic adhesins are history of pelvic tuberculosis infection, appendicitis, inflammatory bowel disease, pelvic surgery, and endometriosis.
If the Fallopian tubes are blocked distally on the ovarian end, fluid may accumulate within the blocked tubes causing the formation of hydrosalpenges. The accumulated fluid may flow back into the uterus, preventing the implantation of an embryo or leading to miscarriages. In such situations, the dilated tubes filled with fluid need to be removed by laparoscopic surgery before an embryo transfer is performed during in vitro fertilization treatment. If only a single sided hydrosalpinx is present, and the other tube is healthy, natural preganancies may ensue after the removal of the diseased tube.
Uterine fibroids:
Fibroids are benign tumors arising from the muscular layer of the uterus. Some fibroids can cause fertility problems depending on their size and location.
Uterine anomalies:
Congenital uterine anomalies as unicornuate uterus, uterine septum, uterine didelphis may prevent the healthy implantation of the embryo within the endometrial layer of the uterus leading to infertility or repeated miscarriages. Acquired uterine pathologies as endometrial polyps or adhesions fallowing uterine instrumentation may also lead to fertility problems through the same mechanism.
Endometriosis:
Endometriosis is a chronic disease caused by the presence of endometrial cells (cells forming the inner lining of the uterus) outside the uterus. The endometrial cells can be located anywhere in the pelvis, including the ovary, bowels, Fallopian tubes, bladder and other pelvic organs. Endometrial cells, when located outside of their natural environment, cause inflammation, fibrosis and adhesions in between pelvic organs leading to functional and structural defects. When located on the ovaries, endometrial cells form chocolate coloured cysts named as endometriomas, which may decrease the number and quality of eggs within close vicinity of the cyst. The inflammatory condition within the pelvis can damage Fallopian tubes, prevent the transport of the egg and sperm through the tubes, and hamper the implantation of the embryo within the endometrium.
Cervical Factors: Surgical procedures such as conization performed on the cervical region, which is the lower segment associated with the vagina, or constrictions that may develop in the cervix after trauma, can prevent sperm from reaching the egg and thus hinder fertilization. Structures like polyps in the cervical canal can also mechanically contribute to infertility.
Autoimmune diseases
Some patients with autoimmune diseases as Coeliac disease, systemic lupus eritematosus and myasthenia gravis have been found to be more prone to infertility than their healthy counterparts. However, because a direct relationship between autoimmune disease and infertility has not been established yet, immunological tests are not routinely carried out on infertile couples.
Genetic Reasons
Infertile couples are more likely to have structural or numerical karyotype anomalies (trizomy, mozaisism, translocasyon) than fertile couples. The most common anomalies related with infertility are 45, X (Turner Syndrome) in women and 47, XXY (Klinefelter Syndrome) in men. Furthermore, mutations in genes including FSH receptor, LH receptor, FMR 1 and TUBB8 are found to be related with infertility.
Unexplained Infertility
This is the condition in which no obvious problems can be detected after detailed evaluation and testing of couples. Infertility testing is usually limited with the ability to only show structural or quantifiable problems. Tools that enable assessment of quality, function or problems in the molecular level are not yet available and therefore quite often than not, all routine tests may turn out to be normal in a certain group of infertile couples. In such cases, problems in the egg quality, sperm quality or endometrial receptivity that cannot be conveyed with current testing techniques are thought to be present.
The majority of infertile men experience low sperm concentration or quality. Reduced sperm motility is termed asthenozoospermia, abnormal sperm morphology (shape) is teratozoospermia, low sperm count is oligozoospermia, and the absence of sperm in semen is called azoospermia. In a small portion of infertile men, despite normal sperm count, motility, and morphology, pregnancy cannot be achieved, known as idiopathic male infertility.
For sperm production in men, the release of GnRH, LH, and FSH hormones from the hypothalamus and pituitary gland in the brain is necessary to stimulate the testes and ensure testosterone synthesis.
Hypogonadotropic Hypogonadism: Some hormonal or systemic diseases affect the hypothalamus or pituitary gland, reducing the release of LH or FSH. Decreased LH or FSH release can lead to reduced sperm production in the testes and infertility.
Testicular Sperm Production Defects: 70-80% of male infertility falls into this category. Reasons that can hinder sperm production in the testes include past chemotherapy, radiotherapy, or genetic factors like Klinefelter syndrome. However, it is often difficult to identify the underlying cause of testicular dysfunction.
Transportation Problems of Sperm: After being produced, sperm enters specific channels in the testicles to undergo the maturation process. One of the most important structures involved in sperm maturation and transport is the epididymis. The vas deferens helps transport sperm from the epididymis to the urethra, where it mixes with seminal vesicle and prostate secretions. Issues in the epididymis or vas deferens can lead to infertility. Erectile dysfunction, premature ejaculation, and infrequent sexual intercourse (less than twice a week) are other factors that can contribute to male infertility.
Sorry, but I can’t fulfill this request.: Sperm parameters are normal despite the inability to conceive is a diagnosis given to men who cannot conceive, and it is seen in 10-20% of infertile men.
Factors related to the immune system: It has been found that individuals with certain autoimmune diseases, such as celiac disease, systemic lupus erythematosus, and myasthenia gravis, have a higher likelihood of infertility. However, since a direct cause-and-effect relationship between these diseases and infertility has not yet been proven, immunological tests are not routinely recommended for infertile couples.
Genetic causes: The frequency of numerical and structural karyotype anomalies (trisomy, mosaicism, translocation) in infertile couples is higher compared to the general population. The most commonly observed numerical anomalies associated with infertility are 45, X (Turner Syndrome) in women and 47, XXY (Klinefelter Syndrome) in men. Additionally, mutations in genes affecting fertility, such as FSH receptor, LH receptor, FMR1, and TUBB8, have been found to be associated with infertility.
Unexplained infertility:
It is the diagnosis given to couples for whom no cause of infertility can be found after detailed evaluation and investigation. It is generally a condition where problems at the cellular level in egg quality, sperm quality, or endometrial receptivity, which cannot be detected by tests, coexist.
The most important factor to consider when deciding when to start an infertility evaluation is the woman’s age. Diagnostic tests can be performed if pregnancy does not occur after 12 months of unprotected intercourse in women under 35 years old. For women over 35, those with a history of menstrual irregularities, known tubal disease, or suspected endometriosis, evaluation can begin after 6 months of unprotected intercourse without pregnancy. Women with a history of chemotherapy or radiotherapy, or those over 40 years old, can start evaluation without any waiting period.
It is important to evaluate both the woman and the man simultaneously, considering that there may be multiple factors causing infertility in the couples being investigated.
The diagnostic evaluation of couples begins with a medical history. The medical history should pay attention to the duration of infertility, previous treatments, the length of the menstrual cycle, past surgical procedures, medications used, history of previous pregnancies if any, frequency of sexual intercourse, family history of infertility, genetic or metabolic diseases, exercise frequency, and dietary habits.
After taking the history, the physical examination focuses on findings that may cause infertility. Since extremely high or low body weight is associated with low fertility, the body mass index of both partners is measured. In women, factors such as breast development, increased hair growth, and the presence of acne can provide insights into hormonal disorders, while a vaginal examination can detect structural anomalies of the uterus. An enlarged uterus or painful cervical movements during a pelvic examination may indicate fibroids or intra-abdominal infections.
After the physical examination, certain tests are requested from the couple.
The most basic of these tests are as follows:
If an underlying cause for infertility can be identified, a treatment strategy targeting that specific cause is implemented. Couples are also advised to make lifestyle changes to enhance fertility, such as quitting smoking, avoiding excessive coffee and alcohol consumption, and maintaining a healthy diet.
Possible treatments include medication, surgical treatment, intrauterine insemination (IUI), or in vitro fertilization (IVF).
Ovulation Problems: For patients with ovulation problems due to reasons other than ovarian failure, short-term use of medications like clomiphene citrate or aromatase inhibitors can induce ovulation. In women resistant to these medications, injections containing gonadotropin hormones can stimulate the ovaries and induce ovulation. For ovulation problems due to high prolactin levels, dopamine agonists can be used to induce ovulation.
Tubal Blockage and Hydrosalpinx: In cases of infertility caused by the blockage and fluid accumulation (hydrosalpinx) in one of the tubes near the ovary, pregnancy can be achieved by surgically removing the blocked tube or disconnecting the tube from the uterus. Surgery for hydrosalpinx can increase pregnancy rates both naturally and through IVF treatment.
Endometriosis: Depending on the severity of the disease, pregnancy can be achieved by surgically removing endometriotic lesions or directly through IVF treatment.
Uterine Problems: Pregnancy rates can increase after correcting issues such as fibroids near the inner wall of the uterus, endometrial polyps, uterine septum, or adhesions through hysteroscopic or laparoscopic surgery.
In a very small group of infertile men, pregnancy can be achieved through medication or surgical treatment. For the majority of men who are unable to father children, the most effective treatment method is in vitro fertilization (IVF).
Hypogonadotropic Hypogonadism: In cases of hypogonadotropic hypogonadism, where there is a deficiency of LH and FSH hormones released from the brain, gonadotropin replacement therapy can stimulate the testes to produce sperm.
Varicocele: Varicocele surgery may be recommended for men with advanced varicocele detectable by physical examination and who have abnormal sperm parameters or complaints such as pain. However, its effectiveness in increasing the likelihood of pregnancy has not been proven.
Oligozoospermia (Low Sperm Count): In men with a sperm count below normal but with a total motile sperm count of 5 million or more, pregnancy can be achieved through intrauterine insemination (IUI), where a concentrated sperm sample is injected into the uterus. However, due to the relatively low success rate of this method, IVF treatment may be applied after a few unsuccessful attempts. For couples with a lower total motile sperm count, direct IVF treatment can achieve faster success.
Azoospermia: In men with no sperm cells found in the sperm sample, pregnancy can be achieved through IVF using sperm obtained from the testes.
Sperm Transport Defects: In cases of erectile dysfunction, retrograde ejaculation, vas deferens obstruction, or absence, pregnancy can be achieved through IVF.
In vitro fertilization (IVF) treatment is one of the most effective assisted reproductive techniques for infertile couples.
