Infertility

Briefly, sterility is the medical definition of the inability to have children. Infertility, by definition medically, refers to being ‘unable to achieve pregnancy despite the unprotected regular sexual intercourse of a man and a woman for a year’. The ‘regular sexual intercourse’ in this definition refers to the sexual intercourse of a woman 2-3 times s during her ovulation periods.
The word ‘sterility’ or the medical condition of ‘sterility’ is a definition that appeared long before treatment for this condition and might still cause desperation in patients. However, today, as there are treatments for many other diseases, sterility also has numerous therapy options. We, therefore, prefer to use the medical word ‘infertility’ to give correct motivation to our patients. Still, we should also add that we use familiar words daily to be clear and transparent when communicating with our patients.
Although the medical definition of infertility is defined as ‘unable to get pregnant after a year of sexual intercourse’, it should be taken into consideration that this period should be shorter for women over the age of 35 and not longer than 6 months for women over 40. Therefore, if a couple is suspected of infertility, they are recommended to contact a professional as soon as possible. It should be noted that infertility is a treatable disease with newly developed treatment options, the success rate of infertility treatment is higher, and the solution to the issues is faster when the treatment plan is made timely.
Infertility can be primary or secondary. While primer infertility is the condition where the couple has never achieved any pregnancy and does not have children, secondary infertility defines the condition where a couple has a prior history of pregnancy or already has children. The condition of infertility developed afterwards.
One frequently asked question on infertility is “Is a person infertile since birth, or can a person be infertile afterwards?”. As with many other diseases, both scenarios are possible; a person might have been infertile since birth or may have acquired the condition afterwards. The important approach here is the correct determination of the reason for infertility. Accurate determination is the key to correct treatment.

While there are differences between countries, the average infertility around the globe is about 10%. 80% of couples willing to have kids can achieve pregnancy in the first 6 months, 10% can achieve in the second 6 months, and 10% are unable to get pregnant after 12 months, facing infertility. While it is also possible that couples who were not able to get pregnant in the first 12 months can also get pregnant afterwards, the rate of success is very low, and we advise our patients to get the consultation of an infertility professional without further delay.

Another frequent question we hear from our patients is, “What age does infertility occur?”. There isn’t a specific age when infertility can occur, and it can happen to any adult. However, it is essential to note that the woman's age has a significant effect. Infertility rate in women increases with higher age. While it is not as substantial as in women, deterioration in the reproductive system can also be seen in men with increasing age. For example, the infertility rate of a couple in their 20s is under 10%, while this number is 14% for a couple in 30-35 age range, 20% for a couple in 35-39 age range, and 25% for a couple in 40-45 age range. As the egg reserve of the woman decreases when she is closer to menopause, the rate of infertility rises.

In all infertility cases, the rate of those where male infertility is the only infertility is 30%, while this number is 40-50% for cases where female infertility is the only infertility. Cases where both males and females have infertility are 20-30%. In a nutshell, while 50-60% of infertility cases are observed due to male infertility, 60-90% of the cases are due to female infertility. Therefore, a couple’s infertility examination should be made for males and females rather than only males or females. This enables a better understanding of the reasons behind their infertility, and therefore, more successful treatment plans can be made, which bring a higher success rate.

If a couple is well informed about the possible reasons for their infertility before the investigation, there’s a better understanding of what needs to be done and why. Based on this approach, we would like to assess male infertility reasons before we continue with information on male infertility tests.
There might be various reasons why sperm production or transportation is affected in male patients:

1 - Pretesticular causes
The issue here is the problem with hormones in the brain, which facilitate sperm production to the testis. So the problem is not with the male’s testis or the canals to transport the sperm, but instead with the hormones that control and facilitate the whole system. These problems might be congenital, such as Kallmann Syndrome or Idiopathic Hypogonadotropic Hypogonadism, but might also occur later in life, such as due to brain tumours, muscle-toning medications that contain testosterone or anabolic steroids, high prolactin hormone levels, or diseases of the thyroid gland. In these cases, sperm production can be restarted with hormonal therapy and with supporting medication.

2 Testicular causes
In this group of diseases, the problem is within the testis itself. Despite the successful order of “produce sperm and testosterone”, sperm and testosterone are not produced due to structural issues of the testis. These diseases might be since birth, such as Klinefelter Syndrome, chromosomal abnormalities like Y-chromosome microdeletion, and undescending testes that lead to insufficient maturing of the testes. The reason might also be acquired later in life due to infections such as mumps orchitis, medications used for muscle toning and hardening of the penis, physical damage on the testes, exposure to toxic materials and some systemic diseases that damage the testicular tissue and impair sperm production. In addition, smoking, regular alcohol use, body-building, obesity and stress also have adverse effects on sperm production in men. Smoking during pregnancy is shown to have a negative impact on the testicular development of the baby and might lead to infertility in the upcoming years.
Another disease that affects the testes is varicocele. Varicocele is a condition where the testes veins in the testicular sac are wider than usual. This causes increased blood flow to the testes and, therefore, increases the temperature of the testes. When the testis is exposed to higher temperatures, it might get damaged. Other factors that cause temperature increases in the testis (such as tight underwear and pants, sitting for prolonged periods, and working in hot environments) similarly damage sperm production in the testes.
As testicular deficiency causes failure in the production of sperm, the advised treatment for these patients is In Vitro Fertilisation (IVF) treatment with sperm donation. Still, if any solid reason as to why testes deficiency occurred is not found and if there are doubts about hormone analysis, a testis biopsy can be made where a sample of the testis is taken and observed. If this observation leads to the discovery of sperms, these sperms can be used. Otherwise, the treatment should continue with sperm donation.

3 Post testicular causes
The issue here is with the canal system of the testes after sperm is produced. This canal system not only transports the sperm but also involves the maturation of the sperm. Therefore, any issues with the canal system of the testes affect the transportation and quality of the sperm. This might be due to diseases present since birth, such as cystic fibrosis, but might also develop later in life due to physical damage to the canals, the tying of the tubes, or infection. Additionally, operations of the inguinal hernia or the varicocele are often not made correctly and might cause damage. For issues regarding the canals, it is possible to obtain the sperm with surgical procedures. Thus, it is advised to try to achieve a test tube baby with surgically collected sperms (with methodologies such as TESA, TESE, micro TESE, PESA, and MESA based on the patient's medical history). In case of infection, treatment is advised for the patient's general health, although this treatment often does not repair the damage to the canals.

In almost half of the cases, despite all the scans and examinations, a solid reason why a patient has sperm issues is not found. Treatment options are present for those when a reason is established.

Infertility in women can be observed in all women and can be seen in later ages as well as young ages. There are many items on the list of ‘infertility causes in females’:

1 Ovary problems
The most frequently seen issue with female infertility is the case where ovaries do not work up to standards and, therefore, cannot provide egg development. As ovaries are very complex structures, there are many mechanisms why they might not be operating correctly.

Ovary reserve depletion: Females are born with a certain number of eggs and spend these over their lives. As the eggs get very low in number and lose quality, menopause occurs. As egg production does not develop later in life, the depletion of egg reserves is irreversible. In some genetic diseases, such as Turner Syndrome and some special conditions where the eggs are damaged, the egg reserve in the ovaries decreases rapidly and might lead to early menopause. In these cases, it is advised that the IVF treatment for a test tube baby takes place with egg donation.
Polycystic ovary syndrome (PCOS): While in normal female ovaries, the most suitable egg is matured, in PCOS cases, a particular egg cannot be grown and used, and in time, this leads to the accumulation of half-matured eggs on the ovary, making further ovulation even more difficult. Due to this occurrence, polycystic eggs can be seen in the ultrasound examination of these patients. In these cases of ovulation problems, the patient is given the correct medication based on her medical condition, and ovulation is restarted. In addition to the medication, Intrauterine insemination (IUI) or In Vitro Fertilisation (IVF) can be performed to increase the success rate.

Hypothalamohypophysial causes: In these patients, due to insufficient working of the ovaries, which are stimulated by the brain, not enough mature eggs are developed. The reason for this issue might be adequate hormones produced by the brain, brain tumours, obesity (excessive weight), anorexia (abnormally low weight) and intensive stress. In these patients, a successful pregnancy can be obtained by treatment with correct hormone therapy.
Hormonal problems regarding other organs: Hormone issues regarding organs other than ovaries can sometimes be overlooked. The hormone prolactin, which is also known as ‘milk hormone’, can cause irregular ovulation if it increases when there is no breastfeeding. Similarly, hormonal deficiencies concerning the thyroid gland can also cause ovulation issues. For a successful pregnancy, it is required that the issues regarding these types of hormonal problems are fixed in advance.

Despite all the scans and examinations, the exact reason why a female cannot ovulate might not be discovered. These cases are mainly because the ovaries cannot receive the ovulation order the hormones receive and cannot respond.

2 Problems with ovarian (fallopian) tubes
Uterine tubes make the connection between the ovaries and the uterus and, therefore, should be investigated while scanning for the causes of infertility.
One of the main observed issues is when the fallopian tubes are blocked, or wider than usual, or excess liquid accumulation in the tubes leads to hydrosalpinx or pyosalpinx. These are signs of damage in the fallopian tubes and are mainly due to previous infections or surgical operations. However, it might also be congenital, although this is relatively rare. The infections that affect the tubes can be sexually transmitted diseases such as chlamydia infections or gonorrhoea that the female has been exposed to during a part of her life. Still, there might also be diseases that are not sexually transmitted, such as tuberculosis. These infections progress silently in the intra-abdominal area and often do not cause any symptoms, and patients frequently do not know when they contracted this infection. In addition, blockage in the tubes or widening of the tubes is not one of the observations that can be made during a regular gynaecological exam (while liquid accumulation is). Based on this, the answer to the question of “Can infertility be seen on ultrasound?” cannot be a definite yes. For an evaluation of the tubes, initially, a doubt needs to arise, and later, the tubes should be analysed with a diagnosis tool such as hysterosalpingography or sonohysterography, depending on the patient's convenience. Additionally, non-invasive surgical operations such as laparoscopy can also be done to observe problems with ovarian tubes.
As there are two uterine tubes, infertility occurs when both tubes are affected. Fallopian tube opening surgery is an inconvenient operation with a success rate of 10-20%. Therefore, an IVF treatment is preferred instead of surgery. In cases where tubes are much wider than usual, the infected liquid accumulated in the tubes flows into the uterus. Therefore, the tying of the tubes or removal of the tubes might increase the chance of a pregnancy in the treatment of a test tube baby.

3 Uterus problems
The uterus is the organ where a baby attaches and grows, so the uterus must be observed in detail when reasons for infertility are being investigated. In these investigations, the most essential part of the uterus is the inner lining, the endometrium. If this lining does not develop well, the baby cannot attach to it. Issues with the uterus can occur since the birth of the female patient (congenital) or might have developed later in her life. Examples of congenital cases are not having a uterus, having an underdeveloped uterus and a faulty development of the uterus (such as a divided uterus, medically named as uterine septum). Examples of cases that develop later in a patient’s life are polyps or fibroid formation in the uterus, damage to the uterus during an operation (majorly during fibroid operations) or removal of the uterus, and development of stuck points in the uterus called synechia due to infections or abortions made in unsanitary conditions. These infections might be due to sexually transmitted diseases or might be due to non-sexually transmitted diseases such as tuberculosis. Some problems with the uterus can be seen via ultrasound, while for others, hysteroscopy, laparoscopy, or open surgery (invasive surgery) might be required.
Corrective surgical operations can help fix the sticky parts of a uterus. They can also help correct some developmental issues that have been present since the patient's birth. In cases where the patient does not have a uterus or has diseases that are not reversible and cause definite obstacles to pregnancy, the wish to have a baby can be fulfilled via the tube baby treatment with a surrogate mother.

4 Problems regarding the cervix
A cervix is an organ that provides the connection between the uterus and the vagina and can be seen with an ultrasound. Blocking of the canals in this organ due to trauma or infections is called ‘cervical stenosis’ and causes infertility as sperm cannot pass through these canals. Additionally, the cervix produces a mucus-like liquid, which enables healthier sperm to be transported inside. Issues regarding this mucus might cause infertility if it does not allow any sperm to travel inside. These problems are frequently seen as a result of hormonal problems, but cervix anomalies might also be present in a female since her birth and might be blocking the sperm’s transport to the uterus.
The blocking in the cervix can be treated via surgery, and the problems regarding the mucus can be treated with hormonal treatments. For all cervix problems, other solutions for achieving pregnancy might be 1-intrauterine insemination (IUI) (or artificial insemination), where sperm is placed in with a special catheter that passes through the cervix, or 2-in vitro fertilisation (IVF).

5 Peritoneum problems
In this group of patients, the most frequently seen problems are endometriosis and immune system problems. Endometriosis is the presence of endometrium, or the uterus wall, in places other than inside the uterus. This tissue grows and bleeds every month during the female menstrual cycle. This is called a ‘chocolate cyst’ or ‘endometrioma’ when on the ovaries. Endometriosis takes place in the ovaries and is dangerous for sperm, egg and also the embryo during pregnancy due to some toxic materials that it produces. In previous years, surgical operations were thought to be efficient in the treatment of endometriosis; however, nowadays, it is not the go-to treatment option as a complete treatment cannot be achieved due to the spreading character of endometriosis, and surgery, therefore, does not increase the success rate of pregnancy in patients.

6 Problems regarding the immune system and the coagulation system
This disease group has recently been diagnosed with the latest technology and is still being researched. Some immune system-related diseases might see the sperm and the embryo as ‘foreign’ and might, therefore, attach these structures. Some of these symptoms show early in life, such as lupus. However, many immune system issues might develop without any visible symptoms. If recurrent therapy of a couple is not leading to a successful pregnancy, observation of immune system issues might increase the chance of success.

Issues regarding coagulation of the blood might be causing the baby to not successfully attach to the uterus due to blockage of the thin veins feeding the baby. Most of these cases are genetic mutations in the female that are present since birth. Failure of a pregnancy despite recurrent treatments might be due to these mutations, and scanning the mutations can increase the chance of success.

• Low amount of muscle tissue (due to testosterone hormone deficiency)
• Low amount of moustache or beard, or having no hair (due to testosterone hormone deficiency
• Fat deposition on hips, similar to a female (due to excess oestrogen hormone)
• Milk production in the breasts, medically named galactorrhoea (due to excess prolactin hormone)
• Constant sleepy behaviour, dry skin, feeling cold (due to thyroid hormone deficiency)
• Not being able to sleep, excess sweating, swollen eyes, flutters in the heart (due to excess thyroid hormone)
• History of undescended testicle (due to testosterone hormone deficiency)
• Low libido or sexual desire (due to testosterone hormone deficiency)
• Burning sensation while peeing, wound in the genital area, pain, or swelling (due to sexually transmitted diseases and damage in the canals)
• Physical damage to the genital area (due to the effect on the testes)
• History of operation on the genital area, especially history of varicocele surgery (sperm production following the surgery can sometimes get better, but may also decrease)
• History of chemotherapy (due to effect on the testicles)
• Testicles smaller than normal
• Low amount of semen (due to problems in canals)
• The semen being a colour other than off-white (due to sexually transmitted diseases and damage to the canals)
• Shortness of breath, being quickly tired, not being able to gain weight since the childhood of the patient (due to the absence of canals based on cystic fibrosis)
• Problems of erection and ejaculation (due to insufficient ejaculation of sperm)

• Hot flushes (due to depletion of egg reserve)
• Late menstruation (due to problems with ovulation)
• Having excess hair, acne, oily skin (due to excess testosterone hormone and polycystic ovary syndrome)
• Milk production in the breasts, medically named galactorrhoea (due to excess prolactin hormone)
• Constant sleepy behaviour, dry skin, feeling cold (due to thyroid hormone deficiency)
• Not being able to sleep, excess sweating, swollen eyes, flutters in the heart (due to excess thyroid hormone)
• Not having any menstrual periods (menopause, failure with ovulation or absence of uterus)
• Not having hair in the genital area (due to oestrogen and testosterone deficiency)
• Under-developed or absent breasts (due to oestrogen hormone deficiency)
• Vaginal discharge with bad smell, abdominal pain, fever (due to damage to the tubes, uterus or cervix based on sexually transmitted diseases)
• Menstruation that continues for too long and with high quantity (due to uterus and hormonal issues)
• Having too painful menstruation or dysmenorrhea (due to structural issues of the uterus, endometriosis, or sticky structure of the abdomen)
• Repeating loss of pregnancies (due to genetic issues, infection in the tubes, issues with the uterus, issues with the immune system or the coagulation system, based on problems of milk hormone or thyroid hormone)
• Having pain during sexual intercourse or dyspareunia (due to endometriosis, issues with the uterus, structural problems or having sticky structures in the abdomen)
• Unable to have sexual intercourse, or vaginismus (due to not being able to have frequent sexual intercourse)

A question we frequently receive from our patients is ‘How is infertility diagnosed?’ or How is sterility examined?’. In this section, we will briefly review what an essential evaluation includes.

The first evaluation should begin with the medical history of the couple. This history should either be taken by an infertility specialist, or forms that an infertility specialist has made should be filled out in detail. The requested tests might be incomplete or unnecessary without knowing the patient's medical history. They might cause the patients extra tiredness and a prolonged research period, leading to the inability to make the correct diagnosis.

The infertility story should contain a wide range of information, such as the biological age of the couple, infertility period, history of pregnancy, menstrual period regularity, chronic diseases, smoking if the couple is blood relatives, history of operations, allergies, family history and childhood history.

Following the medical history, the female patient should undergo a complete physical and gynaecological examination. If male infertility is considered, male patients should also be thoroughly examined physically and urologically.

The infertility examination of the female patient is done by a gynaecologist who specialised in infertility. This examination is a routine vaginal examination where the reproductive organ vagina and the inner reproductive system cervix are examined. During this examination, it is checked by the infertility specialist if it is possible to enter the uterus via the cervix. A smear can be taken to scan for infections. Taking the smear is a pain-free process. Additionally, the uterus, cervix and ovaries are checked in detail via a vaginal ultrasound device, and any other causes of infertility are observed. The observation is not made abdominally but rather vaginally because vaginal ultrasound enables a more detailed evaluation of the reproductive system.

The infertility examination of the male patient is made by urology, where the outer genital system is examined, any wounds or reasons that might prevent pregnancy are observed, both testicles are examined for their size, level and any additional structures in the sacs, and the complaints in the medical history are taken into consideration.

Many tests can be made for infertility diagnosis. However, not every test might suit every female and male patient. Here, tests that can be done for basic research for both female and male patients are summarised.

Before the evaluation of the ovaries is explained, it will be helpful to know basic information about ovaries to understand what is made and why. Ovaries are the egg reserve of female patients. Every woman is born with a limited number of eggs and spends these eggs throughout her life, either by ovulation or elimination. Following the exhaustion of high-quality eggs, the female patient enters menopause. While women are born with an average of 1 million eggs, some patients might be born with a lower amount of egg reserve due to genetic diseases or stress while in their mother’s womb. Some patients might spend their egg reserves faster due to damage to their ovaries. For these reasons, every patient’s egg count versus her age might differ.

Three primary markers determine the condition of eggs in the ovaries:

Age of the female patient, number of antral follicles (little cysts with eggs in) in the ovaries, as seen with ultrasound, and hormone analysis.

Ultrasound

The presence or absence of cysts or mass structures in the ovaries is essential, as any lesion in the ovaries might also affect egg development. As previously mentioned, the number of antral follicles is also crucial. Every female has an egg reserve, which is regularly matured and used. These eggs that have entered the maturation phase become visible in the ultrasound and are seen as antral follicles. These liquid-filled mini-cysts contain an egg, and it is vital to know their number per day. Previously, follicles under 10mm were being counted, but this has recently been changed to 5mm, as these represent eggs that are just about to develop, and the number of these is a better guide. If follicle development is visible but ovulation is not present, ultrasound shows many old follicles that have stopped developing at a stage. These follicles fill the ovaries; the condition is called polycystic ovary, which should be treated. If follicles are absent or very low in number, this hints at decreased egg reserve. If the size of the ovaries is reduced, this hints at the insufficient working of the ovaries.

Hormone analysis:

In the hormone analysis for ovary evaluation, various hormones are assessed. FSH, LH, and E2 hormone tests could be enough for patients who are expected to have a high egg reserve. A more detailed evaluation is required for patients over age 35 with low antral follicle count in the ultrasound. The most sensitive of these evaluations is the AMH test or antimüllerian hormone. Another hormone test, the progesterone test, is done after expected ovulation, and high numbers show successful ovulation.

Other than these tests, prolactin hormone and thyroid hormone tests should also be made as these can damage the regular working of the ovaries. If thyroid gland diseases are suspected, more detailed tests, such as free T4 and free T3 hormone tests and thyroid antibody tests, should be performed. If some other diseases are suspected, for example, rare diseases such as those regarding the adrenal gland, inhibin-B, DHEA-S, 17-OH Progesterone, free testosterone tests could be additionally done, and the overall results of these tests taken together are essential.

Patients with good egg count but ovulation irregularities can benefit from various medications and develop eggs. In contrast, patients with depleted egg reserves or low-quality eggs can benefit from in-vitro fertilisation with egg donation. In a nutshell, only an ultrasound evaluation of the female patient cannot assess the egg reserves, but all scans and exams represent a meaningful outcome.

Dynamic tests:

Clomiphene citrate challenge test or GnRH analogue stimulation test are dynamic tests that show the response from ovaries after known doses of medicines are given to the patient. Several follicles that started maturing can be determined by frequent ultrasounds following the administration of the medication on a known day of the menstrual cycle, and this can give an assessment of the egg reserve and the response to drugs.

A healthy uterus is a vital organ for baby development. The inner lining of the uterus, the endometrium, is required to thrive with the effect of the hormones and provide suitable conditions at the correct time for a baby to hold on. Tubes form the connection between the ovaries and the uterus and, therefore, provide the transport of the egg and the sperm and of the embryo (cellular phase of a baby) that forms after the egg and the sperm meet. As a result, any issues regarding the uterus or the tubes can affect the formation or continuation of a pregnancy.

Various methods are used for the evaluation of tubes and the uterus. While some tests can only evaluate the uterus, others can assess both. While some consider the empty inner space of the organs, some methods evaluate the outer parts. Based on this, the specialist doctor can only determine the test required to assess the patient's infertility. Below is a short description of these methods and how and why they are done.

Ultrasound: During an ultrasound, the most critical evaluation is the inner lining of the uterus or the endometrium. The embryo, which is the cellular phase of the baby, holds on to the endometrium, and the development of this lining is therefore crucial. The endometrium's thickness and appearance can give a lot of information. Additionally, structural problems such as myoma or polyps of the uterus and the proximity of these with the uterus's inner lining can be seen via ultrasound. Unless the tubes are too wide, they are not evaluated via ultrasound, as this method cannot determine if they are blocked. Therefore, ultrasound cannot be the only method used to assess infertility.

Hysterosalpingography (Uterus x-ray):

Hysterosalpingography is one of the fundamental tests that is done for patients who are starting with infertility analysis. Some information taken from the internet can create unnecessary fear in the patients looking for answers to their questions. As this is a sensitive subject, we have made a question-answer section for a detailed description of a uterus X-ray:

What is a uterus x-ray? It is an X-ray made especially for the uterus's inner lining and tubes.

Why is a uterus X-ray made? It is made to observe any problems in the uterus or cervix that may be since birth or may have developed later in life, any blocking in the tubes or any widening of the tubes based on deterioration, and the determination of whether the tubes are open.

Where is a uterus x-ray made? It is made in the radiology department of a hospital or a radiology clinic. A gynaecologist or a radiologist can make it. However, it is advised that a gynaecologist makes it as this is more convenient for the patient.

How is a uterus X-ray made? The patient lies down on a hard bed in the gynaecological examination pose. An instrument named a speculum, also used during routine gynaecological examination to observe the cervix, is placed. Following this, Rubin's cannula injects a contrast liquid into the cervix, which will be visible in the x-ray. This liquid initially fills the uterus and afterwards fills the tubes, and a tiny amount leaks into the abdominal cavity. A couple of abdominal X-rays are made during the passing of this liquid. The whole process takes about 10 minutes.

Is uterus x-ray painful? Uterus X-rays may be slightly painful due to the stabilisation of the cervix and the leakage of the contrast liquid into the abdominal cavity. However, this pain is most of the time similar to the pelvic pain that a female experiences on the first day of menstrual period and lasts for about half a minute to one minute. Therefore, with additional medication before the process to lower the pain and relax the inner organs, the pain that the patient experiences can be minimised. Still, some patients might have a low pain threshold, and in this case, the process might be done while the patient is under sedoanalgesia, a light form of anaesthesia.

When is a uterus X-ray made? Hysterosalpingography can technically be performed at any time other than the patient's menstrual period. During the menstrual period, the blood and the clots can lead to wrong results and might cause the blood in the uterus to repress to the abdomen, preventing the x-ray. Another factor that should be considered is that the X-ray is not made following the ovulation. This is based on the fact that, although minimal, there is still radiation caused by the process, and if the patient is pregnant right after the x-ray, this radiation might also affect the cellular phase of the baby. As the radiation level is low, it is not required to end the pregnancy. However, it is always better to plan to prevent any risks caused to the mother and the baby. The specialist doctor will plan the most suitable x-ray time based on your ovulation period.

Sonohysterogram or Hysterosonogram
What is a sonohysterogram or a hysterosonogram? Another test used in the infertility investigation of patients is a sonohysterogram, also named a hysterosonogram or saline infusion sonogram. It shows similarities with hysterosalpingography.
How is a sonohysterogram made? Similarly, the patient is positioned in the gynaecological examination pose, and a liquid is inserted into the cervix via a technique that is simpler than during a uterus X-ray. As this liquid fills the uterus, it can be observed via abdominal ultrasound. It can show structural damage on the uterus lining wall that might be congenital or may have happened later in life. A sonohysterogram is therefore performed in combination with an ultrasound. This can be done in the examination room, but a radiography scan is not done. Thus, this technique is sometimes preferred. However, ultrasound cannot give an idea about the structures of the tubes, or if these tubes are blocked or not, and therefore, it cannot provide an overall result like hysterosalpingography. For this reason, a sonohysterogram can not replace an ultrasound x-ray.

Hysteroscopy:

Hysteroscopy is a type of operation that uses a camera inserted in the uterus via the cervix. It is used for patients where standard ultrasound evaluation and ultrasound x-ray do not give a definitive outcome or, if there is suspicion of an issue regarding the uterus's inner lining, to observe the uterus lining more clearly and to fix the problem, if possible. It is done in an operating room, and the patient is put under anaesthesia. It enables examination of the uterus's inner lining; however, it does not give an observation of the outer uterus or the tubes.

Laparoscopy:

Laparoscopy, also named minimally invasive surgery (MIS), is a surgical methodology made with the patient under anaesthesia and enables precise observation of abdominal organs via camera. The reason it is called ‘minimally invasive’ is that the abdomen is not cut but instead punctured with a couple of holes. With this technique, the uterus and the tubes can be seen, and any issues can be fixed. This technique also enables observation of the pathologies regarding the ovaries. In previous years, laparoscopy was a process suggested to all infertile couples; however, with today’s technology, it is only done to patients that require the process and therefore, unnecessary surgery is prevented.

Curettage or endometrial biopsy

The uterus's inner wall, or the endometrium, is crucial for obtaining pregnancy. For repetitive unsuccessful treatments, repetitive miscarriages, and cases that show irregularities in the endometrium, taking a sample from the endometrium or cleaning the endometrium can be helpful for diagnosis and treatment. Based on what's suspected, the extracted material can be evaluated for pathological conditions, infections, or immune system-related issues. For example, suppose the patient is suspected to have chronic endometriosis or long-term infection of the uterus's inner wall. In that case, the only way to make a definitive diagnosis is to create a biopsy of the uterus. Similarly, polyps in the uterus's inner wall can be removed with this method.

Infertility is a condition that can be seen together with genetic diseases, especially for patients who have depleted their egg reserve much earlier than expected. Additionally, some congenital developmental diseases of the uterus can also hint at genetic diseases. Genetic analysis should be made for patients with repetitive unsuccessful treatment history, repetitive miscarriage history and if the patient has repetitive genetic anomalies in her embryos. Genetic testing for infertility could be chromosome analysis or scanning of one specific gene suspected of causing the issue, for example, investigation of mutations in the gene that produces coagulation factors if there is an issue with the patient's blood coagulation. What’s crucial is the presence of any suspicion of the specialist doctor for genetic diseases following the interview and the examination of the patient. For this reason, making the correct scans for the proper patient and correct consultation significantly increases the success rate.

This group of analyses aim to investigate if the general health of the female patient is suitable for a pregnancy. Especially for patients with severe illnesses in their history or those who are over 45 years of age, these general evaluations can determine possible issues before pregnancy. They can facilitate the forming and continuation of the pregnancy.

These general evaluations include the determination of the blood type of the patient, liver enzyme tests such as AST and ALT, kidney tests such as urea, creatinine and BUN, tests regarding diabetic conditions such as blood sugar and HbA1c levels, body-mass index of the patient with measurements of height and weight of the patient, and evaluations that can be taken from other disciplines such as internal diseases and cardiology to see if any conditions are preventing pregnancy. The law in Northern Cyprus requires the female patient to undergo these general evaluations if she is over the age of 45 and is going to receive in vitro fertilisation therapy.

In addition, the female patient needs to be scanned for some infectious diseases before pregnancy that are important both for the mom and for the baby. These scans include hepatitis B, hepatitis C, syphilis, toxoplasmosis, rubella and CMV (cytomegalovirus).

Cervical smear analysis of the female patient is also one of the tests that is advised before pregnancy.
In the patient's smear sample, a chlamydia (chlamydia trachomatis) antigen or anticore test is only done when there is suspicion. As both tests are not very trustworthy, choosing the proper test for the right patient is essential.

“How is male infertility diagnosed?can be answered with a sperm analysis or a spermiogram. It can sometimes be stressful for the male to give a sperm sample and have it evaluated; therefore, here we have a question-answer section in detail to describe all that needs to be known about sperm analysis:

Where is sperm analysis made? Sperm analysis can be made in advanced regular and andrology laboratories in IVF centres. In regular laboratories, a laboratory assistant in an in vitro fertilisation centre performs the test, and an embryologist conducts this. As an embryologist specialises in this area and has more experience evaluating sperm, the tests an embryologist performs are considered more trustworthy. Still, in laboratories that frequently make sperm analyses, laboratory assistants make their evaluations based on the most recent criteria.

How do you give a sperm sample? If the patient can give a sperm sample on his own, it is provided via masturbation. The surroundings where this sample is given are essential. As the evaluation of the sperm analysis will take place in the first 20 minutes, it is preferred that the patient provides the sample in the laboratory where the review will take place. If the sample will be given at the patient’s home, it should be placed in a sterile cup previously provided to the patient and brought to the lab in a maximum of 30 minutes. Bringing samples from further distances can disturb the results and misdirect the doctor. For samples that had been brought after more than 1 hour, some evaluations cannot be made, and if the duration is longer than 3 hours, sperm movement analysis will give wrong results. Therefore, it is preferred that the sperm sample be given at the unit where evaluation will take place. IVF centres and advanced laboratories have designated rooms for patients to provide sperm samples. This room generally contains a couch, DVD, TV, magazines to make the sample-giving process more manageable, and a shower. If the patient has difficulty giving the sample independently, his partner is also allowed in the room.

When the sterile cup is given to the patient, the duration of sexual abstinence and the name of the patient is recorded on the cup. Ideally, the duration of sexual abstinence is 2-4 days, with a maximum duration of 7 days. Abstinence longer than 7 days does not lead to correct results. Therefore, patients must be careful about the duration of their abstinence. The vital issue to take into account while giving the sperm sample is to collect all the ejaculation liquid in the cup. Ejaculating outside the cup affects the amount of semen and can cause faulty results for factors such as sperm count. Another element to take into account is that nothing else gets into the cup where semen is placed. Therefore, products affecting the sperm, such as lubricant or soap, should not be used in the process of giving a sperm sample. After the sample is placed in the cup, it is either left in a special box in the room or given to the laboratory assistant or the embryologist.

How is a sperm test made? Sperm analysis begins right as the patient delivers the cup. The initial analysis is for the physical properties of the semen, such as amount, colour and smell. An analysis of the duration sperm follows is liquefied, otherwise known as liquefaction duration. It is checked if there is any coagulation in the semen. Some chemical attributes are evaluated, such as fructose content of the semen and pH. Detailed analyses made to evaluate sperms in the semen sample include sperm count and concentration, sperm motility, sperm structure and sperm vitality. Additionally, the presence of immature sperms and immune system cells called leukocytes is determined, and if they are present, their concentration is measured. Overall, sperm test evaluation is a detailed process that takes a couple of hours.

What are the normal values of a sperm analysis? The normal values of a sperm analysis are determined by the World Health Organization (WHO) and often updated. Therefore, the centre that does the analysis must use the latest information. The latest update by WHO was made in 2010; the values are summarised below.

Sperme valuation:Total sperm count should be above 39 million, and sperm concentration in 1 ml should be a minimum of 15 million. For the evaluation of sperm motility, the ratio of those that move forward at a fast and slow pace should be a minimum of 32%, and the ratio of those that are mobile and stable should be a minimum of 40%. Sperm vitality should be a minimum of 58%. Considering sperm structure, normal sperm should be a minimum of 4%. Additionally, sperm cells should stick together and display coagulation.

Physical and chemical evaluations regarding the semen are as follows: Semen amount should be 1.5 ml or above. Ph should be a minimum of 7.2, the concentration of leukocytes should be less than 1 million per ml, and the liquefaction duration should be less than 1 hour. Zinc, fructose and glucosidase levels in the semen should be over a specific limit.

How are the sperm test results interpreted? Any values outside the norms are considered sperm test defects. For every sperm problem, a second analysis should be made to evaluate if there is a permanent problem, as some conditions might affect sperm production and maturation temporarily, and what is observed in a study might not be observed a day later.

A decrease in sperm count is named oligozoospermia or oligospermia, the condition of having no sperm cells is named azoospermia, the condition of having no semen is named aspermia, and the condition wherein the initial analysis, sperm is not seen, but it can be found after centrifuging the sample is named cryptozoospermia or cryptospermia. Low sperm motility is named asthenozoospermia or asthenospermia, the condition of having a low amount of cells with standard structure is named teratozoospermia or teratozoospermia, and the condition of low sperm vitality is named necrozoospermia or necrospermia. Additionally, these conditions can co-exist. For example, the condition where both sperm count and motility are low is called oligoasthenozoospermia or oligoasthenospermia. The condition where both sperm count and normal sperm ratio are low is oligoteratozoospermia oligoteratospermia. The condition where both sperm count, sperm structure, and motility are low is named oligoasthenoteratozoospermia or oligoasthenoteratospermia, otherwise named OATS syndrome.

As the reasons behind every condition are different, an infertility specialist should interpret sperm analysis results, and the condition that is suspected should be investigated in detail before going on with the treatment, if possible.

What is functional sperm? Another question frequently asked is the frequent sperm concentration. Especially for intrauterine insemination (IUI), it is essential to count the sperms that move forward; this number should be over 5 million. If this number is below the desired count, IUI chances will be meagre, and therefore, the patient is advised to have IVF treatment instead of IUI.

What is a sperm function test? This test is different compared to sperm analysis and focuses on the functionality of sperm cells by investigating if the sperm has the features that will enable it to have the ability to fertilise. Tests such as the postcoital test and the in vitro mucus penetration test investigate if the sperm can penetrate the mucus at the cervix area. The zona binding test examines if the sperm can penetrate through the zona layer around the egg. Another test group is those that evaluate the genetic structure of the sperm (sperm DNA damage test), and the TUNEL test is the most popular one where the ratio of sperm with damaged DNA structure is determined. For IVF and ICSI treatments, it is not required that the sperm penetrate the mucus or the zona layer. Therefore, these two tests are not valid for patients requiring these treatments. However, in some cases, it is still informative to know sperm DNA integrity.

If there are issues with sperm production of the male patient or if there is a suspicion of hormonal deficiency, a hormone analysis could be requested. Investigation of FSH, LH and testosterone hormones in the male patient could give an idea about whether the problem is from the testicles or another issue. Additionally, deficiencies regarding prolactin or the milk hormone and TSH thyroid hormone can also affect sperm production; therefore, these hormones can be scanned. If there is suspicion of an issue regarding the thyroid, free, T4 and free T3 hormones (other hormones involved in the thyroid gland) and thyroid antibodies could also be investigated.

Some genetic diseases can have a significant impact on sperm production in male patients. As these diseases can be transferred from generation to generation in years, they might not only cause infertility. Still, they might also be the root of the problem for many family members. The genetic analysis should be certainly made for recurrent IVF failure, for cases where sperm cannot fertilise the egg or where the embryo development falls behind, for recurrent embryo genetic anomaly history, for recurrent miscarriage of the partner, and for cases where infertility history is present in the family. Genetic tests included in the infertility investigation could be chromosome analysis, Y-chromosome microdeletion analysis where the Y chromosome (the male chromosome) is investigated for any missing genes or a single gene scan analysis if there is suspicion regarding diseases that occur due to a single gene. Another investigation is for the ratio of sperm DNA damage directly in the sperm sample by genetic analysis. There is also an analysis called the FISH test, where numeric problems of specific genes in the sperm are analysed. All in all, ‘Can the sperm diagnose infertility?’ is not a question that can always be answered with a yes. While not all tests need to be done for a patient, the necessary tests must be determined by an infertility specialist who can correctly evaluate the patient’s information. Correct analyses allow patients to be steered correctly and allow correct treatments.

If the sperm of the male patient will be used in the treatment, it is routinely checked for some diseases to prevent contagion of the infection to the lab, the female patient, and the baby. The diseases that are routinely checked are Hepatitis B, Hepatitis C, HIV and syphilis. Additionally, other information, such as the blood type of the male patient, could be requested. As some infections during sperm production could also be transmitted to the semen, diseases such as Chlamydia and Gonorrhea can be scanned if it is suspected during sperm analysis or due to patient evaluation.

An emotional breakdown and psychological pressure is often observed in infertile couples. Initially, as the couple tries to keep this a secret from their family and people around them, it causes severe pressure, which may often lead to depression, anxiety, panic issues, anger and communication problems between the couple. Sexual intercourse may turn into a mission; couples could start blaming each other and feel inadequate, and this might lead to unnecessary tension for the couple, who is already going through a tough time. It is frequently seen in male patients that they refrain from talking about this subject or going to a specialist in infertility psychology.

If the broad family of the couple is informed about the issue, they might also get involved in the subject, which causes severe pressure on the couple, who is already worn out. The couple who is under infertility psychology could stay away from all pregnant women and people with kids, could become lonelier under these feelings of inadequacy and anger feelings and might feel like everything is losing its meaning.

In all the investigation and treatment duration, there are some reasons why couples abstain from receiving consultation. These do not feel like they need consultation, do not want to talk about the subject, and worry that they will be pitied or angry. Based on these, the ratio of couples who receive consultation support before and during the treatment is only 20%, and it is observed that these couples are exceptionally compatible and are exposed to less stress. Stress is a significant issue, especially for patients receiving treatment for the first time, young couples and patients who are dealing with infertility for a long time.

Other than the psychological effects of infertility, infertility treatment also has psychological effects. While both male and female patients go through an increase in sincerity and hopefulness during the production and transfer of the embryo, there is an increase in stress levels following the treatment during the period when they wait for the test day. If pregnancy successfully occurs, the issue will be resolved on its own. However, in cases where pregnancy does not happen, both male and female patients could show depression signs. These signs could continue for about a month for the male patient and increase up to 6 months for the female patient if no preventive cautions are taken. This will be a vicious cycle for the female patient and might lead to her not making another step in the treatment, although she still has the chance of getting pregnant.

The treatment period of the couple also shows a wide range of emotions. While stress is not a factor that directly lowers the chance of success, the stress hormones lower the treatment compatibility and focus and might affect success. Lowering the amount of stress increases success performance. Therefore, receiving correct support and guidance not only during infertility investigation but also during the treatment and afterwards increases the success rate up to 15% and allows couples to get over this period with the least amount of burnout. While the patients receive medical support from their doctors, it is therefore vital that they receive emotional support and guidance from a consultant that they trust.