Causes, diagnose and treatment of infertility

Causes of infertility

GETTING PREGNANT DOES NOT ALWAYS HAVE TO BE SO EASY

 

Did you know that the human species has one of poorest reproduction capabilities  among all the animal species living on planet Earth?

The chance that a young and fertile couple will conceive a baby during unprotected sexual intercourse in a single month is only 17 percent, and after the age of 35 it declines even further.

 

When is the right time to get a check-up?

 

If you have been trying to get pregnant unsuccessfully for over a 12-month period. A woman after  age of 35 as early as after 6 months, and after the age of 40 you do not need to wait longer than 2-3 months of unsuccessful attempts.

 

WHAT MAY THE PROBLEM?

 

When searching for causes of infertility it is very important to realise that this is a problem of the couple, not a purely male or female problem. Thinking of infertility as a shared issue is natural, since conceiving a baby requires both of you. This perception may also help you to easier overcome this difficult period and allow you to become closer to each other, not grow apart.

Besides the typical causes related to reproductive organs or sperm, infertility can also be caused by hormonal disorders, genotype disorders or immunology factors, not to mention an unhealthy lifestyle, which often influences our life more than we are able to realise.

Every couple is unique, and so is the diagnosing and addressing of any issue. Thus, there is no universal blueprint for how to conceive a much-desired baby. All the processes are set-up individually to reflect your needs.

 

How we can help

Look at the frequently asked questions of our patients or ask a question yourself


Diagnosing

Problems with getting pregnant can have numerous causes. Identification of the cause is usually the first step towards solving the problem. In the Gyncare centre for assisted reproduction we therefore pay maximum attention to comprehensive diagnostics.

In the search for the causes of infertility, we pay attention to immunology, genetics, sexology, and last but not least, psychology, too. Naturally, it is not always necessary to go through all of the above check-ups and examinations. Thanks to their long-standing experience, our experts often identify the cause of the problem early on, at the beginning of the whole process.

 

The physician should know these answers

After the basic diagnosis, the physician should know the answers to the following essential questions:

  • Does ovulation take place?
  • Does the women have a sufficient ovarian reserve?
  • Does the women have patent (i.e. passable) fallopian tubes?
  • Does the woman have adequate thyroid gland function and prolactin and insulin production?
  • Does the partner’s semen analysis parameters meet the conditions sufficient for spontaneous conception of a baby?
  • Does the women suffer from endometriosis?

The diagnosis usually moves on only after answering these essential questions that identify the most frequent causes of infertility. If, however, experts come up with ‘negative’ findings from the above examinations, they keep searching. In the next step, they examine potential causes from the perspective of immunology, genetics, sexology or andrology.


Diagnosing the FEMALE

Initial examination

When diagnosing infertility in the Gyncare centre for assisted reproduction, we closely cooperate with your gynaecologist. The results of previous examinations are very important.

We want to look at your overall health. Therefore, besides examining your hormonal profile or the patency of fallopian tubes, we would like to know if you experience a lot of stress and wish to know more about your overall lifestyle.

 

Hormonal profile examination

A hormonal profile examination takes place simultaneously with a sonography examination (folliculometry). It represents a complete mapping of a single menstruation cycle, in which we conduct three hormonal examinations from blood samples and a small pelvis sonography examination.

  • TESTING OF OVARIAN RESERVE
    • By determining the concentration of gonadotropic hormones, we can identify what your ovarian reserve is. The examination is done on the second or third day of your menstruation cycle.
    • The anti-mullerian hormone level, or AMH, is an even more precise indicator of the ovarian reserve. It can be determined on any day during the menstruation cycle.
  • SONOGRAPHY EXAMINATION (FOLLICULOMETRY)
    • With sonography, we identify the presence of a maturing follicle (where an egg with the ability to mature and be released from the ovary should be present) on the ovary and the height of the mucous membrane – the epithelium on the uterus – which should be approximately 8 mm at that time. The examination is conducted on approximately day 12 to 13 after the beginning of menstruation.
    • At the later stage of the cycle (day 21 after the beginning of menstruation) we will conduct a sonography examination once again. A yellow body (corpus luteum), which develops from the follicle from which the egg was released during ovulation, is present on the ovary. The epithelium of the uterus is also changed as a result of the influence of progesterone, the hormone from the yellow body. Besides sonography, we will also take a sample of your blood to determine the level of progesterone and prolactin.
  • FURTHER TESTING
    • At any stage of the menstruation cycle, we carry out a sample collection to determine the TSH  (thyroid-stimulating hormone) level, the insulin level in patients with polycystic ovaries syndrome (to rule out the non-reactivity to insulin, which leads to ovulation disorders), the vitamin D level and male hormones (androgens), or perhaps other examination depending on the physician’s indication.

Examination of fallopian tubes patency

Examination of the patency of fallopian tubes is most often conducted in two ways. A laparoscopic examination represents the standard and is conducted under full anaesthesia. During the examination a special optical device is applied into the abdomen, and the surgeon can directly see how the reproductive organs look and simultaneously, he or she can rule out endometriosis. The examination is conducted either during hospitalisations or as a one-day outpatient surgical procedure.

Sonography examination of fallopian tube patency (Hystero salpingo contrast sonography, shortened to HyCoSy) is conducted as an outpatient procedure without anaesthesia. A thin catheter, through which a contrast agent that is visible on the sonography is applied, is inserted into the cervix. The physician can see whether the contrast agent is able to pass through the fallopian tubes and reach the ovaries. This examination is not optimal for every patient; for example it cannot be applied to rule out or confirm endometriosis (which can only be confirmed via a laparoscopic examination).


Diagnosing the Male

Initial examination

Semen analysis can only be conducted after a 3- to 5-day sexual abstinence. Semen analysis parameters can be different at each examination or testing; therefore, the data is assessed in a comprehensive manner, taking into account other tests and examinations. The chance for fertilization can be fully excluded only if there is no sperm in the ejaculate. Otherwise, the limit when spontaneous conception is not possible cannot be determined. However, the worse the parameters of the semen analysis are, the less likely it is going to be adequate for spontaneous conception.

 

The essential examination provides the following:

  • Volume, look and the ejaculate liquefaction time
  • Sperm count (the number of sperm per millilitre)
  • Sperm motility and morphology examination

 

Specialised ejaculate testing:

  • Trial wash test – separation of sperm from the seminal plasma (i.e. other parts of the ejaculate). Depending on how much sperm we get, we can make a better decision as to which method of assisted reproduction is most suitable.
  • Examination of sperm antibodies in ejaculate – if antibodies are present in the ejaculate, the chance of spontaneous conception is lower even if the basic semen analysis examination results are all within normal levels.
  • HALOSPERM – sperm DNA integrity test, which determines the presence of sperm with a damaged genotype, as this sperm has a lower ability to fertilise the egg.
  • Oxisperm – test for diagnosing sperm damage by oxidative stress. Recommended for smokers, males with varicocele (enlarged veins near the testicles), obesity and negative external influence.
  • Vital Test – differentiation of dead and live motionless sperm. During standard semen analysis, we cannot differentiate whether the sperm cells are alive but lack energy for motion or whether they are dead.

Diagnosing the couple

Initial examination

The postcoital test is the examination of mucus samples collected from the cervix following unprotected sexual intercourse. It is conducted during ovulation, when the mucus has the optimal characteristics for sperm penetration. The mucus is examined under the microscope right after the sample is collected.

The following characteristics are assessed:

  • Sperm count
  • Sperm motility and its quality

The results point to the ability of sperm cells to penetrate the mucus of the cervix and to survive in this environment. In the case of a high percentage of motionless sperm cells, the factor causing this problem may be sperm antibodies, which result in their motionlessness in the case of clustering. Such clusters are alive, but they prevent sperm from moving and thus block their ability to fertilize the egg. Before the planned examination, 3-day sexual abstinence is recommended to ensure optimal sperm quality. The post-coital test is a simple, quick, pain-free and affordable examination, which enables the physician to determine whether the couple has a real chance of conceiving a child in a natural way.


Treatment

When nature seems to fail, we at GYNCARE are able to help you. We use state-of-the-art treatment procedures and take advantage of the most efficient instruments to achieve the much desired and belated result.

How we can help

  • Inducing ovulation
  • Intra-uterine insemination (IUI)
  • IVF (in vitro fertilisation) — native cycle / soft cycle / standard in vitro fertilisation

Methods used for IVF

Micromanipulation techniques of egg fertilisation by a sperm:

  • Intracytoplasmic sperm injection (ICSI)
  • Intracytoplasmic morphologically selected sperm injection (IMSI)
  • Physiological intracytoplasmic sperm injection (PICSI)
  • Oosight spindle view

Sperm sorting techniques:

  • Magnetically activated sperm sorting (MACS)

Embryo culture techniques: 

  • Prolonged embryo culture
  • Embryo culture in Embryoscope
  • Embryo culture in multi-chamber incubator
  • Embryogen – culture medium

Additional methods:

  • Laser-assisted hatching (AH)
  • Embryo glue
  • Cryopreservation – freezing of sex cells and embryos

How we can help

Inducing ovulation

Normally, ovulation (i.e. release of the mature egg from the ovary) is a regular and spontaneous process. However, if the egg is not released from the ovary, the woman cannot get pregnant. Inducing ovulation is one way to help such women to get pregnant.

Ovulation can be induced by way of preparations ensuring the growth of the follicle in which the egg is maturing.

You may attempt to get pregnant at home, ideally before your ovulation begins. Inducing ovulation can also be linked to intrauterine insemination (IUI).

The average success rate of this procedure: We manage to induce ovulation in as many as 90% of spontaneously non-ovulating women. However, the chance of getting pregnant can also depend on other factors.

When is the procedure recommended? Inducing ovulation is indicated in women who do not ovulate spontaneously and in whom we do not suspect another cause of infertility.

 

Intrauterine insemination (IUI)

Intrauterine insemination (IUI) is an insemination process, during which we insert sperm cells directly into the uterus just before ovulation. Quality sperm will thus get into the immediate proximity of the egg and the chance for fertilisation increases.

This is a simple procedure that takes only several minutes. IUI can take place as a part of the natural menstruation cycle or you may (following the recommendation of a physician) undergo hormonal therapy, during which we will monitor the growth of follicles on ovaries via sonography. After the procedure, you only need to wait and after a certain time suggested by the physician, try a pregnancy test.

The average success rate of the procedure is 12-15% per single treatment cycle, i.e. per menstruation cycle in which the procedure is carried out.

 

When is the procedure recommended?

  1. Light forms of endometriosis with patent (i.e. open) fallopian tubes
  2. Light semen analysis disorders
  3. Idiopathic infertility
  4. Impossible vaginal sexual intercourse
  5. Unsuitability of vaginal sexual intercourse (infectious patients – e.g. in case of HIV positivity)
  6. Usage of donor sperm

 

Standard IVF cycle

In vitro fertilisation (IVF) is a laboratory technique in which the egg is fertilised outside the woman body. IVF represents one of the most efficient ways to deal with the issue of infertility.  

IVF usually takes place by way of intracytoplasmic sperm injection (ICSI), when the sperm is applied directly into the egg. The advantage of this method is that only a single sperm is sufficient.

The fertilised egg is cultured, and after some time it is placed into the uterus, where, in an ideal case, it implants successfully and further develops.

IVF can be performed by using the following combinations:

  • An egg and a sperm cell from the couple
  • An egg from the female partner and a sperm cell from a donor
  • An egg from a donor and a sperm cell from the male partner
  • An egg and a sperm cell from donors

The average success rate of the procedure: Currently, the success rate of IVF cycles is somewhere in the neighbourhood of 50 to 60% per cycle. However, it is necessary to emphasise the difference of success rate in the respective age brackets. While up to the age of 30 the likelihood of success is very high, exceeding 60%, after the age of 40 it declines to a level of 15%.

 

When is the procedure recommended?

There are numerous indications for performing IVF; the following are the essential ones:

  1. Non-patent fallopian tubes, fallopian tubes are not present – following a surgical excision
  2. Pathological parameters of semen analysis
  3. Endometriosis of the woman
  4. The threat of ovarian function failure
  5. Genetic indications
  6. Immunological indications
  7. Idiopathic infertility – unexplainable infertility, in which we cannot identify the cause of infertility, even after the women undergoes 2-3 IUI cycles

 

Native cycle and soft cycle

In native and soft cycle, we deal with a procedure similar to standard IVF. The difference is that in native cycle the in vitro fertilisation takes place without hormonal stimulation, and in soft cycle hormonal stimulation is shorter and the doses are lower compared with classic stimulation.

  1. Native cycle is an in vitro fertilisation without hormonal stimulation, during which the physician will retrieve an egg from a naturally matured follicle.
  2. Soft cycle takes place in a similar manner, but before the egg is collected, the patient is hormonally stimulated. However, the doses are smaller and the stimulation is significantly shorter in comparison with standard IVF.

The next steps are the same as in IVF for both types of cycles. In vitro fertilisation takes place in a laboratory, followed by embryo culture and its transfer into the uterus.

The average success rate of the procedure: Success of soft cycles is reported at approximately 15-17% per stimulation. The cumulative success ratio after 3 cycles is approximately 30%. There are no precise statistics on the success rate of native cycles; in general, the ratio is relatively low in this case – below 10% per cycle.

When is the procedure recommended? With respect to their very low success rate, native cycles are rarely recommended to patients. Soft cycles are either selected by patients themselves, in case they refuse to go through the standard hormonal stimulation, or by patients who refuse cryopreservation (freezing) of embryos and want to fertilise a very small number of eggs. Equally, in individual cases, soft cycles are suitable for patients at a higher age or perhaps patients with non-optimal reaction to standard stimulation.


Methods used in IVF

Micromanipulation techniques of egg fertilisation by a sperm

ICSI – Intracytoplasmic sperm injection

ICSI represents application of a sperm cell directly inside the egg (into the cytoplasm). During a standard ICSI, the embryologist selects the sperm depending on its motility and morphology; however, special methods of selecting the right sperm also exist.

When should this method be used?

  1. In the case of insufficient sperm count in ejaculate or insufficient sperm motility
  2. In severe semen analysis pathology
  3. After surgical collection of sperm
  4. If a female patient is older than 37
  5. If we are unable to obtain enough eggs
  6. If the women suffers from endometriosis
  7. If sperm antibodies are present in the ejaculate
  8. If sperm DNA is fragmented

IMSI – Intracytoplasmic Morphologically Selected Sperm Injection

Sperm selection method in ICSI, which is based on maximum microscopic enlargement of the sperm. This is a modification of the ICSI method, when the embryologist can assess the minimum defects of sperm morphology and select the optimum sperm for egg fertilisation. The IMSI method cannot be used in the case of a very low sperm count in the ejaculate.

PICSI – Physiological Intracytoplasmic Sperm Injection

Sperm selection method in ICSI, which is based on selection of a mature sperm cell. Before the actual ICSI, sperm cells are layered over a plate, which is similar in composition to the egg cell coating. Only sperm cells that have adequate genetic characteristics and would stand the best chance of actually fertilising the egg should then become bound firmly to this plate.

When should this method be used?

  1. In patients with pathologic semen analysis parameters
  2. In non-optimal development of embryos in preceding IVF cycles, if we anticipate sperm-related problems
  3. In repeated unsuccessful IVF cycles with embryotransfer of quality embryos

Oosight spindle view

A special microscopic technique, which enables imaging of the egg spindle, which then enables better evaluation of egg quality. It is recommended in females aged over 37 with low AMH levels, in females who have had inadequate embryo development in the preceding IVF cycle despite the standard semen analysis parameters, in eggs which have non-optimal microscopic image, in applying frozen eggs and in women with a low percentage of fertilised eggs in the preceding IVF-ICSI cycle.

Sperm separation techniques

MACS – Magnetic-Activated Cell Sorting

A sperm-sorting method, which uses the influence of a magnetic field. It results in separation of sperm cells with a good genotype (undamaged DNA), which stand the best chance of fertilising the egg. Apart from IMSI and PICSI, sperm cells separated in this manner can be used in all methods of assisted reproduction – insemination, IVF, ICSI or this sperm can even be frozen for further usage in the future.

 

Methods used in IVF

Embryo culture methods:

Extended embryo culture (up to day 5 of embryo development)

Embryo culture in laboratory conditions up to the stage of the expanded blastocyst, which develops on day 5 after fertilisation. IVF results following the blastocyst transfer are better compared to embryo transfer at earlier stages of development, as the development of a major part of embryos stops right after day 3 following fertilisation. If the embryo development reaches day 5, there is a greater chance of implantation in the uterus.

Embryo culture in EmbryoScope

A special culturing device for embryos, which maintains stable conditions in the incubator and provides output in the form of a video recording of embryonic cell division (the device takes photos of the embryo every 20 minutes). The embryologist can thus precisely state the regularity of embryonic cell division. The result of this culturing is then the possibility of optimal selection of the embryo to be transferred into uterus (i.e. the embryo with the most regular cell division), without disrupting the conditions for cell division.

Embryo culture in a multi-chamber incubator

When embryos are cultured in a multichamber incubator, each patient has a tiny incubator chamber dedicated only to her embryos. Compared to classic culturing, it is therefore not necessary to disrupt the optimum atmosphere, which is essential for correct embryonic cell division, every time the embryologist needs to control the embryos of another patient. The stable atmosphere in the incubator improves early embryonic development, thus increasing the chance for implantation in the uterus and further development.

Embryogen – culturing medium

A special culturing medium designed for patients who have suffered repeated miscarriages in the past (pregnancy losses). It contains specific growth factors, which increase the percentage of embryos with optimal cell division. Besides patients with repeated pregnancy loss, it is also recommended for patients who have suffered from repeated failure of embryo implantation following the transfer, as well as patients with idiopathic infertility.

 

Additional methods:

Laser-assisted hatching (AH)

Disrupting the embryo shell with a laser beam. Up to day 6 following fertilisation, the embryo is protected by a special shell – the zona pellucida. It needs to leave this coat to be able to implant itself in the uterus. An embryo shell which is too firm can be the reason why the embryo cannot leave and is therefore unable to implant itself in the uterus. Cutting the zona pellucida with a laser beam is safe and poses no risk to further embryonic development.

Embryo glue

Embryo glue is a lay term for a specific medium (solution) in which the embryo is transferred into the uterus. The chemical composition of this medium is very similar to the liquid that is normally found in the uterus and has a greater density compared to the standard media used for embryo transfer. This should provide not only optimal conditions for further development and embryonic cell division but should also minimise the risk of embryo shift within the genital tract of the woman following the embryo transfer.

Cryopreservation – freezing of reproductive cells and embryos

The process of freezing reproductive cells and embryos has become an integral part of assisted reproduction methods. This is a procedure in which reproductive cells or embryos which are not directly used for fertilisation or injection into the uterus are frozen at temperatures as low as -196 °C. This enables their preservation for a practically unlimited time.

  • Cryopreservation (freezing) of oocytes

Under this method, oocytes (eggs) are frozen; it is applied in women who are awaiting oncological treatment or in women who do not plan pregnancy at the given moment and wish to keep their eggs preserved for the future (so called social freezing). Cryopreservation of eggs is preceded by hormonal stimulation of ovaries, which takes approximately 12 days. Sampling of mature eggs is conducted under total anaesthesia, and the collected eggs are immediately frozen and kept in liquid nitrogen. Cryopreservation is carried out by way of vitrification – ultrafast cryopreservation of eggs in special straws (capillaries).

  • Cryopreservation (freezing) of embryos

If multiple embryos are obtained in the IVF cycle, we transfer only one or a maximum of two embryos with optimum development into the uterus. The remaining embryos are recommended to be frozen and preserved for the couple for the future. The survival rate of embryos after thawing is high, and the couple thus stands a good chance in the case of failure to get pregnant during transfer of the fresh embryo to go through the procedure of cryoembryotransfer (CET), which is preceded only by preparation of uterine mucous membrane to adopt the inserted embryo. The woman does not need to again undergo the whole stimulation process followed by egg collection. In the case of good embryo quality after thawing, chances are good for pregnancy after a cryoembryotransfer similar to the transfer of fresh embryos.

  • Cryopreservation (freezing) of sperm

Cryopreservation of sperm is used in patients before initiating oncological treatment as well as in a sperm donor program. Sperm survival rate after thawing is highly individual, but in general, the process of freezing and thawing is survived by approximately 50% of sperm cells. Depending on the parameters of semen analysis, sperm cells can be used after thawing either for intrauterine insemination, when the insemination dose should contain at least 15 million sperm cells. In the case of worse semen analysis parameters, eggs are fertilised using micromanipulation techniques within the IVF program.


Donation

A donor program is an integral part of comprehensive infertility treatment.

Oocyte (egg) donation

Oocyte donation belongs among the successful methods of infertility treatment. Treatment with donated eggs represents a set of therapeutic procedures, when the eggs of an anonymous donor are fertilised by sperm of the partner or a donor.

Reasons for treatment with donated oocytes:

  • Early failure of ovarian function
  • Genetic disorders
  • Low quality of eggs in previous IVF cycles
  • Previous oncological treatment
  • Repeated unsuccessful embryo transfers with own eggs

In as many as 50% of oocyte recipients the reason is the premature ovarian insufficiency, ovarian function failure before reaching the age of 40

Oocyte donation principle

Oocyte donors are women aged 18 – 34. The actual donation is preceded by a whole range of examinations and tests, which the donor needs to undergo to rule out infectious, sexual and genetically transmitted diseases. When selecting an oocyte donor, the appearance and phenotype characteristics of the beneficiary are taken into account. Equally, we also attempt to consider the blood group of the beneficiary and the donor.

The oocyte donor undergoes ovarian stimulation, which is followed by egg retrieval under total anaesthesia. On the day of collection, these eggs are fertilised by the partner’s sperm and after several days of culturing (typically 3 to 5 days), based on agreement with the beneficiary, 1 or perhaps 2 embryos are transferred into the uterus of the beneficiary. Transfer of the embryo(s) is scheduled so that the cycle of the beneficiary is harmonised with the donor’s cycle. In some cases, embryos are frozen, and then harmonising the donor’s and beneficiaries’ cycle is not necessary. The embryo transfer takes place in the natural cycle on a specific day after ovulation is confirmed.

Oocyte donation is strictly anonymous, voluntary and unpaid. However, every donor is compensated for her time and the costs she may have incurred in relation to the donation of eggs. As laid down in the Slovak legislation, the mother of the child is the woman who gives birth to it.

Embryo donation

Embryo donation is an alternative form of infertility treatment suitable for and used by couples in which both partners suffer from significant disruption of developing their own reproductive cells (eggs and sperm). Treatment with donated embryos uses embryos created by fertilisation of an egg from an anonymous donor with sperm from another donor.

Sperm donation

 

Sperm donation is recommended to couples where the male partner has a continuing problem with fertility. This can mean an absence of sperm in ejaculate (azoospermia) or cases when the male partner carries a genetic disorder.

Donated sperm may not be used for fertilisation of a woman that has no partner.

Sperm donation principle

Any man aged 18 to 34 can become a sperm donor provided that he meets the required criteria in terms of semen analysis parameters and that the results of initial examinations and tests rule out infectious, sexually and genetically transmitted diseases. Sperm will be frozen and stored in quarantine for 180 days; tests for infectious and sexually transmitted diseases are then conducted again. Only when negative results are confirmed can the sperm actually be used in donor programs.