INTERNATIONAL HOSPITAL IVF Center



Infertility

Evaluation of infertile couples
Methods to evaluate presence of ovulation
Tuboperitoneal Reasons
Unexplained infertility
Treatment options in Infertility
IVF / ICSI
Controlled ovarian hyperstimulation
Sperm retrieval by invasive techniques for ICSI procedure
Indications of sperm retrieval with invasive techniques
Sperm retrieval from reproductive tract by invasive techniques for intracytoplasmic sperm injection (ICSI) procedures
Techniques that can be used to obtain sperm by surgical intervention
Indications of sperm retrieval by surgical interventions
Alternative treatment options to surgical sperm retrieval techniques and advantages, disadvantages, risks and complications of these techniques
Risks, complications and results of sperm retrieval by surgical techniques
Duration of a TESE procedure, total duration o your stay at the Hospital
Things that should be considered (at home, at work) after TESE


Infertility
 Infertility is defined as the inability to conceive during one year of unprotected regular sexual intercourse. The chance for a normal couple to obtain pregnancy in a single cycle is estimated to be around 20-25%. Depending upon this estimation, it is possible to say that a normal couple can achieve pregnancy with 90% chance at the end of one year. Infertility is a health problem affecting 10-15% of couples. Although it seems that the incidence of infertility has not changed during past years, it is observed that the number of patients evaluated in ART (Assisted Reproductive Technology) clinics has been steadily increasing in years.  Two major sociocultural changes have effect in this increased ART applications. First; advances in ART have attracted media attention and media information raised public awareness about infertility and modern treatment modalities.  Second; sociological changes brought by 20th century modern life style resulted in great numbers of women attempting pregnancy at older ages.
The causes of infertility among couples admitted in ART clinics are:
-20-40% of male factor infertility
-40-55% of female infertility
-10% of both male and female infertility.
In 10% of patients, although all of the standard elements of infertility are evaluated, infertility etiology can’t be found. This group of patients is classified as “unexplained infertility”.

Evaluation of infertile couple
The evaluation of an infertile couple consists of a detailed interview of patient’s infertility history, physical examination, preliminary tests and counseling regarding the cause of infertility, possible treatment procedures, success rates and couple’s expectations. After a detailed assessment of medical and surgical history of a woman, galactorrhea (breast secretion), hirsutism, pelvic pain, dysmenorrhea, dyspareunia, genital tract infections, previous gestations and menstrual cycles are questioned thoroughly. Male partner is questioned about previous genital surgeries (orchiopexy, varicocele surgery), infections especially mumps orchitis and sexual life.
Evaluation of female starts with general physical examination followed by gyneocologic examination
In the physical examination of a woman; body mass index is calculated. Signs of androgen excess and galactorrhea are evaluated and thyroid gland is palpated. Gyneocologic examination consists of pelvic examination and transvaginal ultrasonography. Uterus, endometrium and ovaries are examined. Presence of myoma, endometrial polyp, hydrosalpinge, and ovarian reserve are carefully examined.
Initial basic laboratory tests of an infertile couple are spermiogram, hormone profile and hysterosalpingography. If there is a problem with spermiogram, urology/andrology consultation must be planned. Depending upon all the laboratory tests and physical examination findings, etiology of infertility is defined. The cause of infertility, possible treatment modalities and success rate of each treatment are explained to the couple.
The major causes of female infertility include ovulatory dysfunction (30-40%), tubal and peritoneal pathology (30-40%), and unexplained infertility (10-15%). Few couples have problem of absolute infertility that can be caused by total absence of germ cells or mullerian anomalies (absence of uterus or rudimentary uterus). These couples must be counseled about adoption, donor ovum/sperm use (illegal in our country) and surrogate motherhood.

Methods to evaluate presence of ovulation

Hormone levels;
The level of luteinizing hormone (LH) which is responsible from ovulation starts to increase rapidly 38 hours before ovulation. There are a wide variety of commercial products allowing women to determine the timing of ovulation. Generally known as “ovulation prediction kits” or “LH kits”, these products are all designed to detect the midcycle LH surge in urine. Serum LH levels also confirm presence of ovulation.
Basal body temperature measurement;
Basal body temperature (BBT) is body temperature under basal conditions at rest. As a test of ovulation, daily BBT recordings are based on the thermogenic properties of progesterone; as levels rise after ovulation, BBT also increases. Although it is useful, it is not a frequently used method.
Midluteal serum progesterone concentration;
The increase in the levels of serum progesterone concentration is an indirect indicator of ovulation. Progesterone levels greater than 3 ng/ml that is measured in luteal phase is reliable objective evidence that ovulation has occurred.
Ultrasonographic follow-up;
Follicular growth, selection of dominant follicle and ovulation of dominant follicle can be followed up ultrasonographically throughout the cycle. Appearance of fluid in the Douglas and decrease in size of dominant follicle are accepted as ovulation findings.

Tuboperitoneal Reasons
Tubal and peritoneal pathology is among the most common causes of infertility and the primary diagnosis in approximately 30-35% of infertile couple. Tubal factors are related with damage of tubes and history of pelvic inflammatory disease, septic abortion, ruptured appendix, tubal surgery, and severe endometriosis suggest possibility of tuboperitoneal damage.
HSG is the classical method for evaluation of tubal patency in infertile women. HSG is best scheduled during 2-5 days interval immediately following the end of menstruation. HSG has 85% of sensitivity in defining tubal patency. A water soluble contrast dye is introduced through a catheter inserted into the cervical canal and as contrast substance passes through the uterine cavity and tubes, fluoroscopic films are taken.
Laparoscopy is the golden standard for evaluation of tuboperitoneal factor infertility. Pelvic organs are directly visualized. Pelvic adhesions, presence of endometriosis and tubal patency are evaluated.

Unexplained infertility
Unexplained infertility is diagnosed when all of the standard elements of the infertility evaluation yield normal results (normal semen analysis, objective evidence of ovulation, normal uterine cavity, patent tubes). The incidence of unexplained infertility is about 10-20% in the infertile population.
Unexplained infertility can be considered as the lower extreme of normal distribution of reproductive efficiency. The average cycle fecundity of an infertile couple is about 2-4% which is 20-25% in normal couple.
In these couples, infertility can be caused by problems related with sperm/ovum dysfunctions or problems related with embryo development and implantation of embryo.  All these functional defects can’t be detected by standard methods of infertility work-up. Treatment options are intrauterine insemination, superovulation targeting development of more than one ovum and ART.

Treatment options in Infertility
The most common treatment approaches in infertility;

  • Intrauterine insemination (IUI)
  • In vitro fertilization (IVF)
  • Intracytoplasmic sperm injection (ICSI)
  • The basic aim is to increase the chance of fertilization and pregnancy. The philosophy underlying each of the infertility treatment modalities has 3 components;
  • Superovulation achieved by oral or injected drugs in order to produce many oocytes.
  • Preparation of sperm either for intrauterine insemination or IVF/ ICSI
  • The use of special techniques in order to bring sperm and ovum together.
  • When a patient undergoes an IUI cycle, the development of utmost 3 mature follicles (18-20 mm in diameter) is aimed. The risk of multiple pregnancy increases in the case of development of more than 3 follicles. When the leading follicle reaches 18-20 mm in size, HCG is injected to induce ovulation. 34-36 hours later following the HCG injection, the sperm sample, which is processed in the laboratory in order to enhance its motility and quality, is injected into uterine cavity through a catheter. The pregnancy rate after one IUI cycle is about 8-15%. The drugs used for ovulation induction in IUI cycles are either orally taken clomiphene citrate and letrozole or injectable gonadotropins.
    The doses of drugs used for superovulation in IVF / ICSI cycles are much higher than the ones used in IUI cycles. The aim of an IVF/ICSI cycle is to achieve controlled ovarian hyperstimulation and to collect as much ovum as possible in order to fertilize them in the laboratory conditions. Thus there will be lots of embryos allowing a clinician to select the higher quality ones for transfer and freezing some others.
    Clomiphene citrate was started to use in infertility treatment after late 1950s. It induces FSH secretion from hypophysis to stimulate follicular development.
    Letrozole which is an aromatase inhibitor has been recently started to use for the purpose of ovulation induction but clinical experience related with this subject is limited. Letrozole may be an option for clomiphene resistant cases.
    Injectable gonadotropins have been used for ovulation induction since 1960s. These drugs are used for clomiphene resistant women, in hypogonadotropic hypogonadism cases and in the ART cycles to achieve controlled ovarian hyperstimulation. Since they are quite effective and potent drugs, they have the risk of multiple pregnancy and OHSS. One other disadvantage is that, compared to clomiphene citrate, its cost is increased. 
    For almost 30 years, the only exogenous gonadotropins available were human menopausal gonadotropins (hMG), an extract prepared from the urine of postmenopausal women containing 75 IU of FSH and LH per ampoule. These drugs are prepared for intramuscular injections. With the development of recombinant technologies, recombinant FSH and LH which are designed for subcutaneous use has been introduced into clinical use in the recent years.

    IVF / ICSI
    Assisted Reproductive Technologies (ART) encompasses all techniques involving direct manipulation of the ovum and sperm outside of the human body. IVF and ICSI are two of the most common forms of ART. The indications of ART are as follows:

  • Repeated (3-6 times) failure of ovulation induction
  • Severe tubal disease
  • Advanced endometriosis
  • Severe male factor infertility
  • Unexplained infertility
  • Recurrent pregnancy loss
  • Decreased ovarian reserve
  • In couples who carry autosomal recessive or sex linked genetic disorders or a balanced translocation, IVF with PGD (Preimplantation genetic diagnosis) can be used to avoid the risk of delivering an affected child.
    The philosophies underlying the ART applications are a sequence of highly coordinated steps beginning with controlled ovarian hyperstimulation with exogenous gonadotropins followed by retrieval of oocytes from the ovaries under transvaginal ultrasound guidance, fertilization in the laboratory and finally transfer of the embryos into the uterus.

    Controlled ovarian hyperstimulation;

    There are many ovarian stimulation protocols in ART. The principal approach is to suppress ovarian hormones by down-regulation of endogenous pituitary gonadotropin secretion. GnRH agonists are used to achieve this effect. The stimulation with gonadotropins is started after down-regulation is succeeded. The relatively recent introduction of GnRH agonists into clinical practice has provided another option for ovarian stimulation in ART. In general, the goal is to have at least 2 follicles measuring 19-20 mm in diameter. Once targeted follicular development is reached, HCG (5000-10000 IU) is administered to induce final follicular maturation. Ovum pick-up is generally performed approximately 36 hours after HCG administration.

    Sperm retrieval by invasive techniques for ICSI procedures;
    Azoospermia is described as the absence of sperm on standard microscopic examination. The prevalence of azoospermia is approximately 1% in all men and 10-15% in infertile men. To establish the diagnosis, the semen should be centrifuged at high speed (300 gr for 15 minutes) and absence of sperm should be documented an at least two separate occasions. Azoospermia is generally classified as obstructive (normal sperm production) or nonobstructive (decreased/absent sperm production) azoospermia.
    Sperm can be obtained from male genital tract by a wide variety of techniques;

  • Microsurgical testicular sperm extraction (TESE)
  • Testicular sperm aspiration (TESA)
  • Microscopic epididymal sperm aspiration (MESA) Sperm can be obtained by microsurgical epididymal sperm aspiration.
  • Percutaneous sperm aspiration (PESA).  PESA using a fine needle has also been used for sperm aspiration. Since amount of sperm obtained by this technique is much less, it is not a frequently preferred method.
  • Sperm aspiration from seminal vesicles
  • Diagnostic procedures in the evaluation of azoospermia etiology include;
  • A detailed medical history
  • Urologic examination of testis, evaluation of secondary sex characteristics
  • Evaluation of volume of semen, pH and fructose content
  • Serum FSH and testosterone measurements
  • Genetic tests, karyotype, Y chromosome microdeletions, CTFR gene mutation analysis
  • Transrectal/scrotal ultrasonography
  • Vasovesiculography
  • Testicular biopsy
  • Indications of sperm retrieval with invasive techniques

    1. Azoospermia cases
    2. Obstructive azoospermia

    Surgical correction of obstruction may be tried in obstructive azoospermia cases if it is amenable to treatment. Epididymovasostomy, vazovasostomy operations for proximal obstructions and transurethral ejaculatory duct resection or transrectal aspiration of prostatic cysts can be performed. If the patient is not amenable to surgery or in the case of failure of surgery ; MESA ,PESA or TESA/TESE can be performed to obtain sperm
    -Nonobstructive Azoospermia
      In nonobstructive azoospermia cases there is a problem with the sperm production. The problem may be related with hypothalamic-pituitary axis which regulates spermatogenesis within the testis. Microsurgical TESE is preferred in nonobstructive azoospermia cases because of the risk of obtaining insufficient sperm when TESA performed. It is suggested that mapping before TESE/TESA helps to define the possible sites of spermatogenesis. If the etiology of azoospermia is a pure hormonal deficiency, the hormone replacement treatment before TESE has been conclusively demonstrated to be efficacious. 

    Sperm retrieval from reproductive tract by invasive techniques for intracytoplasmic sperm injection (ICSI) procedures
    Azoospermia is described as the absence of sperm on standard microscopic examination. The prevalence of azoospermia is approximately 1% in the general population and 10-15% in infertile men.

    Techniques that can be used to obtain sperm by surgical intervention;
    • Micro TESE: Sperm retrieval from testis by using open surgery and optical magnification
    • TESA: Testicular sperm aspiration
    • MESA: Microscopic epididymal sperm aspiration
    • PESA: Percutaneous sperm aspiration
    • Vasal sperm aspiration
    • Sperm aspiration from seminal vesicles

    Interventions or examinations used to diagnose aspermia/azoospermia

    To establish the diagnosis, the semen should be centrifuged at high speed (3000 g for 15 minutes) and absence of sperm should be documented in at least two separate occasions. Azoospermia is generally classified as obstructive (normal sperm production) or nonobstructive (decreased/absent sperm production) azoospermia.

    Procedures to be followed in order to diagnose azoospermia

    • A detailed medical history
    • Urologic examination of testis, evaluation of secondary sex characteristics
    • Evaluation of volume of semen, pH and fructose content
    • Serum FSH and testosterone measurements
    • Genetic tests, karyotype, Y chromosome microdeletions, CTFR gene mutation analysis
    • Transrectal/scrotal ultrasonography
    • Vasovesiculography
    • Testicular biopsy
    • Investigation of sperm in the urine

    Findings and the course of Aspermia / azoospermia

    Inability to have a child may be the only evidence in men with azoospermia. If a hormonal dysfunction or a genetic anomaly is the cause of azoospermia, symptoms associated with these problems can also be observed. In some types of obstructions in ejaculatory channels or ejaculatory dysfunctions, the volume of the semen is decreased or no semen can be obtained. The course of azoospermia may differ upon different underlying causes. If obstructive azoospermia is at the level of ejaculatory channel, the volume of the ejaculate can drop down to 0.5-1 ml. In more proximal obstructions no significant changes in ejaculate volume may be seen.

    Indications of sperm retrieval by surgical interventions

    Before intervention, it is necessary to assess the presence of a factor which may prevent the female partner from having a child with assisted reproductive Technologies (ART), or if such a factor exists, she should be undergoing proper treatment procedures. This situation has to be documented beforehand.

    A). In pellet negative azoospermia cases in which no sperm is seen in two subsequent semen analyses even after examination by centrifugation of the ejaculate at 3000g for 15 minutes

    Obstructive causes

    For obstructive azoospermia cases in which an obstruction in sperm conductive channels for various reasons is present, first aim should be to remove the obstruction. By this way, a permanent therapy for future pregnancies is established. For this reason, surgical correction methods should be tried in the first place. For proximal obstruction epididymovasostomy, vasovasostomy; or for distal obstruction transuretral ejaculatory canal resection (TUR-ED) or transrectal aspiration of cysts within prostate should be considered. For cases in which no corrective surgery can be applied or in cases of correction failure, vasal sperm aspiration or sperm retrieval from epididymis (MESA, PESA) should be considered, if none can be applied, sperm retrieval from testis (TESE, TESA) should be applied.

    In cases with obstruction in sperm canals, bilateral absence of vas deferens, and desire of having a child after vasectomy sperm retrieval from epididymis or vas deferens (except cases with the absence of vas deferens) are the ideal methods. In cases with obstruction of distal ejaculatory canals, aspiration of sperm from seminal vesicles depends on clinician’s experience. Although percutaneous sperm retrieval from Epididymis (PESA) and testis (TESA) can be easily applied, since these techniques include blind interventions several possible complications such as hematoma, trauma and atrophy can be observed, retrieved spermatozoa may not be enough for freezing procedure and no tissue sample for histopathological analysis can be obtained. During TESE procedure, probable open surgery-associated complications such as hematoma trauma, atrophy has to be noted. In cases with congenital bilateral vas agenesis, first sperm retrieval from epididymis by PESA or MESA should be tried, when such procedures are not possible or failed, sperm retrieval from testis should be followed.

    Nonobstructive causes

    If inability to retrieve sperm from ejaculate is caused by disruption of sperm production in testis, sperm retrieval from testis is the only treatment mode. At the same time, considering the availability of having biopsy samples as well as the possibility of having not enough sperm during TESA, sperm retrieval from testis by open surgery (TESE) is generally preferred. However, it has been suggested that before performing TESE or TESA, in order to determine the regions with focal spermatogenesis (mapping) and to look for sperm on this locations in the future, diagnostic TESA can be performed. Based on proven results, only in cases with disrupted spermatogenesis due to hormonal failure (hypogonadotropic hypogonadism) hormone replacement therapy should be done before TESE. After hormone replacement, sperm can be seen in the ejaculate, even if it is not, the probability of finding sperm after TESE increases. In azoospermia cases with an associated varicocele, although it is not proven, varicocele operation prior to TESE may increase the probability of successful sperm retrieval.

    B) Cases in which all of the spermatozoa are observed to be immotile during semen analysis

    In this situation, although there are studies showing the extraction of motile spermatozoa from testis, whether sperm from ejaculate or testis is superior over the other is not proven.

    C) Azoospermia cases having insufficient sperm with low semen volume (hypospermia) or aspermia cases

    In azoospermia cases with semen volume is less than 1.5 ml, distal ejaculatory canal obstructions or retrograde ejaculation may be present. If ejaculatory canal obstruction can be treated or spermatozoa with sufficient quality and quantity can be obtained from ejaculation, these spermatozoa should primarily be used for the treatment. In unsuccessful cases or with situations in which this treatment can technically not be applied in cases vesicula seminalis aspiration, vas deferens aspirations, sperm retrieval from epididymis or testis can be followed. In neurogenic-based ejaculation disorders, if sperm retrieval by penile vibration or electro ejaculation is possible, medical treatment can be tried. In cases with unsuccessful sperm retrieval due to lack of erection, erection-ejaculation should be done by medical or intracavernosal vasoactive drug injections. If these methods fail, sperm can be obtained from testis. If the problem is seminal canal obstruction, sperm retrieval should first be tried from vas or epididymis.


    Alternative treatment options to surgical sperm retrieval techniques and advantages, disadvantages, risks and complications of these techniques

    Testicular Sperm Extraction by open surgery (TESE)

    TESE is a surgical intervention. In a TESE procedure where testicular tissue can be examined under microscope, the chance to retrieve spermatozoa is increased by determining and selecting the normal-looking seminiferous tubules showing spermatogenesis. However, if the duration of the procedure is extended, local anesthesia may become insufficient. For this reason, TESE may require general anesthesia. On the other hand, TESA can be done under local anesthesia and the duration is shorter. It does not require microsurgery experience. It may be preferred in cases with high probability of successful sperm retrieval. In non-obstructive azoospermia cases, when compared with TESE, its superiority is currently debated. However, in such cases, TESA can be used for mapping method in order to determine whether sperm is present in the testis or not. In this way, it can be helpful for the sperm retrieval procedures to be performed in the future. The cost of the procedure is less when compared to TESE. On the other hand artery injury may result due to multiple pricking of the testicular tissue. Especially in nonobstructive azoospermia cases, sufficient sperm may not be retrieved both for ICSI and for freezing. One superior property of TESE is that it allows the clinician to perform a biopsy for histopathological examination. In cases where sperm can be retrieved from epididymis or vas deferens, it is not recommended to retrieve spermatozoa from testis by open surgery (Here no confirmed scientific data exist and the experience of the surgeon should be considered). On the other hand, compared to epididymal spermatozoa, testicular sperm may not complete the maturation and this can affect the successful fertilization. Also, the amount of sperm that can be retrieved from testis is less than the one from epididymis. The risk of bleeding and hematoma in the testis is more than during MESA. Although it is not proven, surgical opening of the testis can carry the risk of developing antisperm antibody production. Moreover, the fluid obtained from vas deferens and epididymis is clean and does not contain cells and erythrocytes. This can make the manipulation easier in the laboratory. However, the fluid that is obtained during TESE contains higher amount of erythrocytes and these can make the manipulation more difficult. In cases where epididymis can not be operated for sperm retrieval, sperm should be searched in the testis. In nonobstructive azoospermia cases, testicular sperm retrieval is the first method to be chosen.

    Percutaneous sperm aspiration from testis (TESA)

    It can be done with local anesthesia. It takes shorter. It does not require microsurgery experience. It may be the preferred method in cases in which the chance of sperm retrieval. However, artery injury may result due to multiple pricking of the testicular tissue. If there is an obstruction in the epididymis, it is not possible to correct it. Especially in nonobstructive azoospermia cases, sufficient sperm may not be retrieved both for ICSI and for freezing. In obstructive cases, it does not have an advantage over PESA or vasal sperm aspiration In order to determine the regions of testis where sperm production is present; it can be performed as a diagnostic “mapping method”.

    Hormonal stimulation of spermatogenesis

    It is proven to be effective in only hypogonadotropic hypogonadism cases. In cases with normal FSH and LH hormone levels it is acceptable to stimulate spermatogenesis with the administration of these hormones, however, the beneficial effect of this method is not proven but there exist several case reports with positive results.

    Reconstructive surgery in obstructive azoospermia

    If the reason for not being able to retrieve spermatozoa is related to an obstruction in sperm canals, first attempt should be to correct this obstruction. If failed, other means of sperm retrieval should be performed. The cost of reconstructive surgery is less than the cost of ART. If the obstruction is corrected, the couple can have children by natural conception. For this reason, reconstruction is primarily considered. In men with previous vasectomy history, if more than 15 years have been passed after vasectomy, pregnancy rate can decrease due to the decay in the sperm quality and concentration. In this case sperm retrieval from epididymis and testis can be preferred for IVF/ICSI procedures. Also, after vasectomy, the mean duration that should be passed in order to observe sperm in the ejaculate is 12 months. If the female age is over 37, in order to minimize the time, sperm retrieval from epididymis and testis can be chosen. For women over 40 years, whether it is after vasectomy or natural conception, the successful pregnancy rate is significantly reduced. That is, for the cases in which not more than 15 years have been passed after vasectomy and for cases with no trace of a female factor, reconstructive surgery should be considered. For vasoepididymostomy, not having an older female age and the absence of a known female factor should be considered. The experience of the surgeon is also important when deciding for reconstructive surgery.

    Surgical treatment in the obstructions of distal ejaculatory canals

    If an obstruction in the ejaculatory canals is documented, this should primarily be corrected, however, if there is a failure or the canals is not suitable for the correction sperm can be retrieved by other methods. Together with this, if the female age is above 37, in order to minimize the time that can be spent, one of the other sperm retrieval methods can be chosen for coupling sperm retrieval + IVF/ICSI. For women above 40 years of age, whether by natural conception or by natural way, pregnancy chance in ART for cases that are above 40 is significantly reduced.

    Risks, complications and results of sperm retrieval by surgical techniques:

    1. First of all, in spite of a detailed search, spermatozoa with desired quality and concentration may not be obtained. Even if it is obtained, using these spermatozoa for ICSI can result a chance of pregnancy that can be within limits of 30-40%.

    2. Although this technology can provide an advantage in the treatment in infertile men, these it has to be kept in mind that these techniques are new and their long-term safety has not been established yet. There are evidences indicating the increase in sex chromosome abnormalities in ICSI children. The risk of major congenital abnormality in ICSI children is around 2.4-3.4%. It has been reported that, compared to naturally conceived children (2.1%), children born after ICSI is suspected to have an increased congenital abnormality rate; but these results are under debate. However, this increased rate not only can be due to spermatozoa that can carry structural and molecular defects resulting from inefficient spermatogenesis in nonobstructive azoospermia, but can also be due to the ICSI technique itself. In cases with few spermatozoa obtained but no normal spermatozoa can be produced in testis, there may exist several genetic abnormalities that cause or support this result. 15-20% of azoospermic men carry chromosomal abnormalities, 13% of them have Y-chromosome microdeletions. Several studies show that utilization of sperm cells that can carry these chromosomal abnormalities in such cases may result in lower fertilization and pregnancy rates. However, the possibility that the future child can carry chromosomal abnormalities due to these the usage of these spermatozoa is not certain. Men with Y-chromosome deletions have a risk to inherit these deletions to their future boys. While considering all of these, it is necessary to perform karyotype analysis and Y-chromosome microdeletions analysis in nonobstructive azoospermia, and CFTR gene mutation analysis in cases with bilateral absence of vas deferens before IVF/ICSI. On the other hand, it has to be kept in mind that, even the results of these tests are normal; there is a possibility to experience a chromosomal abnormality in the future child. If both of the vas deferens is palpable, spermatogenesis is normal, azoospermia is due to an obstruction in the canals and there is no evidence of a suspected genetic defect, genetic analysis is not necessary. In cases with advanced maternal age, repeated IVF failures, karyotypic abnormalities, chromosomal translocations and cases with an existed heritable disorders that can be passed on to the next generation preimplantation genetic diagnosis and/or amniocentesis can be required. Pregnancy may be terminated if necessary.

    3. After surgical operation, infections and apses can develop and a long-term antibiotics treatment and sometimes hospitalization may be necessary. Although it is extremely rare due to current advanced techniques, port-infection organ loss can be experienced.

    4. Allergy to the local anesthesia used during operation is a rarely observed complication. Respiration and circulation problems that are associated with general anesthesia can develop. In cases with bleeding disorders, it is contraindicated as in other surgical interventions. Although using a microscope (TESE, MESA) can considerably reduce the risk, scrotal or testicular hematoma and bleeding can be observed. In such cases, there may need a long-term wound therapy, hospitalization or a second surgical operation if necessary.

    5. Excision of large tissue pieces or disruption of blood circulation may result in a decrease in testosterone hormone secreted from testis, testicular atrophy or organ loss. If another TESE operation is planned after the first one TESE, there should be at least 6 months interval between them.

    6. Spermatozoa can be retrieved in > 90% of all obstructive infertility cases showing normal spermatogenesis. In nonobstructive azoospermia cases, the rate of successful sperm recovery is around 57%. Depending on the pathology of the testicular tissue, these rates can vary between 16% and 100%. After sperm is obtained, clinical pregnancy rates are between 30-40%. The rate of success in sperm retrieval may decrease if there exists a previous infection, trauma or disruption secondary to surgical operation.

    7. There isn’t any proven test that can predict a successful sperm recovery. No significant relationship is found between testicular volume, serum FSH level, male age and the possibility of a successful sperm recovery. Although previous testis biopsy can partially help to predict the successful retrieval, it does not have a certain value. In Y-chromosome microdeletions tests, only deletions in AZFb region can be associated with near-zero chance of a successful sperm recovery after TESE. Observation of a palpable epididymis is evidence that favors an obstruction. Moreover, absence of vas deferens during examination, presence of a previous vasectomy or an evidence of an obstruction also shows higher sperm recovery rate if the correct methodology is chosen.

    8. In some IVF/ICSI cases, depending on the hormones used, ovarian hyperstimulation may develop. In such cases, the patient may need to be hospitalized and may require treatment.

    9. In 30-35% of the cases can result in twin pregnancies and in 5-10% of the cases it can result in triplets or higher order pregnancies. Multiple pregnancy carry mortality and morbidity risks along with it. In necessary circumstances, reduction procedure can be considered.

    Who is going to perform

    Procedure has to be performed by experienced urology specialists. For Vesicula seminalis aspiration, radiology specialists may accompany urology specialists.

    Consequences that can arise if the procedure is not accepted:

    Surgical sperm retrieval procedures are not life-saving operations. Therefore, refusing to undergo such operations does not cause health problems. However, it only results in loosing the chance of having a child if not applied.

    Acceptance of surgical sperm retrieval techniques: advantages and possible results:

    The success and reliability of surgical sperm retrieval techniques in men with azoospermia/aspermia in having a child have already been proven. Couples that can not have a child with other techniques can have a child with this technique. In nearly all obstructive cases showing normal spermatogenesis, spermatozoa can be retrieved. However, this retrieval rate can be decreased depending on the presence of a previous infection, trauma or a previous surgery. Depending on the histology of the testicular tissue and a presence of an underlying genetics disorder, these rates can vary between 16% and 100%. Clinical pregnancy rates are between 30-40%.

    Testicular Sperm Extraction by open surgery (TESE)

    In men with inability to produce ejaculate or no sperm is seen in the ejaculate, examination of spermatozoa in testicular tissue by surgery is called “Testicular Sperm Extraction (TESE; testicular sperm retrieval).

    TESE Technique

    TESE is performed with local anesthesia. However, in certain situations where the procedure takes longer than usual, local anesthesia may not be necessary therefore regional or general anesthesia can be chosen. In cases where local anesthesia is used, application of a mild intravenous sedation can be comfortable to both the patient and the surgeon. The purpose of the operation is to select and to remove the seminiferous tubules that are likely to contain spermatozoa. Removed tubules are then transfered to the laboratory and minced, trying to retrieve spermatozoa with sufficient quantity and quality. Studies show that compared to the tissue extraction by naked aye, the use of optical magnification in selecting seminiferous tubules is not only increases the rate of successful sperm retrieval but also decreases the tissue damage by minimizing the disruption in tissue integrity. In this procedure, even if loop (surgical eyeglasses) is used, loop can be insufficient when 20x – 30x magnification becomes necessary. Ideally, operation microscope with at least 20x optical magnification should be preferred.

    Operation starts from the bigger testis. If it is performed under microscope, larger tubules with more opaque-white in color showing normal spermatogenesis are removed. Excised tissue immediately prepared in the laboratory and the operation team is informed about the presence or absence of spermatozoa in this excised tissue piece. If sufficient amount of spermatozoa is not obtained, operation continues for the other areas in the testis. If required, operation also continues on the other testis. The procedure goes on until the maximum amount of tissue volume is reached in order not to disturb the tissue integrity. The purpose is to excise minimum amount of tissue while retrieving sufficient quality and quantity of spermatozoa for IVF-ICSI. Spermatozoa obtained in these procedures can be frozen and stored for future use. However, due to the nature of the freezing technique, up to 50% decrease in survival rate, decrease in implantation, biological risks such as spontaneous mutation can be observed. Studies have shown that freezing does not increase the congenital abnormality rate However, some studies have also shown that compared to ejaculated spermatozoa, spermatozoa retrieved from testicular tissue have an increased chance of developing DNA damage due to freezing procedure. According to our current knowledge, amount of viable spermatozoa may decrease after freezing/thawing, but no difference is seen on fertilization and pregnancy rates is seen when viable spermatozoa is used after thawing. When extremely low quantity of spermatozoa is used for freezing, it has to be kept in mind that viability can totally be lost. For this reason, although freezing of spermatozoa retrieved during a diagnostic TESE procedure can be an alternative, fresh use of testicular spermatozoa retrieved in a TESE procedure performed simultaneously with oocyte pickup procedure should primarily be preferred. If sufficient amount of spermatozoa is retrieved, these can be frozen for a later use. While no difference in pregnancy rates can be seen with fresh or frozen testicular or epididymal spermatozoa in obstructive azoospermia cases, it is not clear whether the same is also true for nonobstructive azoospermia cases.

    Duration of a TESE procedure, total duration o your stay at the Hospital
    The total duration of the operation may take between 30 minutes to 2 hours depending on the unilateral-bilateral nature of the operation, or whether a proper surgical microscope is used or not.

    If local anesthesia is given, the patient should be under observation for 1-2 hours in order to check homeostasis and pain. At the same time, if sedation anesthesia is applied, in order for the patient to recover from anesthesia may be extended. Patients who receive general anesthesia can stay in the hospital overnight.

    Things that should be considered (at home, at work) after TESE
    Patient can stand up after he/she recovers from the anesthesia after surgery. By paying attention not to traumatize the wound, walking and moving is allowed. Since the patient can feel pain during the first night after surgery, oral analgesics can be required. Cases with a unilateral and narrow incision can go to work the next day. Resting at home for 3-7 days is recommended for cases with bilateral or with wide incisions. Cases with clean wounds, by paying special attention not to irrigate the wound, the patient can have a bath the next day. In cases with wounds that are not completely healed, any contact with water should be avoided. In normal conditions, sexual intercourse and heavy activities can be started one week after.

    Luteal phase support

    After embryo transfer, in order to support the development of inner lining of the uterus (endometrium) and a growing embryo, luteal phase support is performed with progesterone (by oral, vaginal or intramuscular administration). If pregnancy is established, this treatment can be continued until the 10th-week of the pregnancy. Pregnancy is confirmed by examining B-hCG level 12 days after embryo transfer. If it is positive, presence of a sac is evaluated after three weeks by USG.

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