Therapy options

This application helps to propose an appropriate fertility therapy method and to find the most suitable clinic worldwide based on the price, duration and legislative options of the treatment in various countries.

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Lifestyle change

Lifestyle is a term to describe the way individuals, family circles, and societies live and which behavior they manifest in coping with their physical, psychological, social, and economic environments on a day-to-day basis.

Lifestyle is expressed by daily work and leisure profiles, including activities, attitudes, interests, opinions, values, and allocation of income. Lifestyle is a composite of motivations, needs, and wants and is influenced by factors such as culture, family, reference groups, and social class.

The leading causes of global deaths today are largely lifestyle related. A healthy lifestyle is an important predictor of future health, productivity and life expectancy. It has been found to reduce the factors which contribute to health risks.

The combination of the main healthy lifestyle factors-maintaining a healthy weight, exercising regularly, following a healthy diet, and not smoking-seem to be associated with as much as an 80% reduction in the risk of developing the most common and deadly chronic diseases.

Lifestyle diseases or chronic diseases are associated with the way a person or group of people lives on a daily basis. In other words, lifestyle diseases characterize those diseases whose occurrence is primarily based on the daily habits of people and are a result of an inappropriate relationship of people with their environment.

Lifestyle is associated with the development of many chronic diseases. The World Health Organization (WHO) has recognized diabetes, hypertension, stroke, diabetes, obesity, high cholesterol, cardiovascular disease and stroke, cancer and chronic lung disease as major non-communicable diseases (NCDs). There are many other conditions associated with modern living like stress, depression and substance abuse are important factors also contributing to lifestyle related morbidity and mortality like suicides. These major NCDs share common lifestyle related risk factors like physical inactivity, unhealthy diet, tobacco use and harmful use of alcohol. Globally, the current scenario of NCDs is the major cause of morbidity and mortality. 

Recently, the pivotal role that lifestyle factors play in the development of infertility has generated a considerable amount of interest. Lifestyle factors are the modifiable habits and ways of life that can greatly influence overall health and well-being, including fertility. Many lifestyle factors such as the age at which to start a family, nutrition, weight, exercise, psychological stress, environmental and occupational exposures, and others can have substantial effects on fertility; lifestyle factors such as cigarette smoking, illicit drug use, and alcohol and caffeine consumption can negatively influence fertility while others such as preventative care may be beneficial. A summary table of each lifestyle and the associated relative risk (RR) and odds ratio (OR) is provided (Tab. 1).

Physical exercise

Physical exercise is performed for various reasons, including strengthening muscles and the cardiovascular system, honing athletic skills, weight loss or maintenance, and merely enjoyment. Frequent and regular physical exercise boosts the immune system and helps prevent the "diseases of affluence" such as heart disease, cardiovascular disease, Type 2 diabetes, and obesity. It may also help prevent depression, help to promote or maintain positive self-esteem, improve mental health generally, and can augment an individual's sex appeal or body image, which has been found to be linked with higher levels of self-esteem. Childhood obesity is a growing global concern, and physical exercise may help decrease some of the effects of childhood and adult obesity. Health care providers often call exercise the "miracle" or "wonder" drug—alluding to the wide variety of proven benefits that it can provide.

With use, muscles consume energy derived from both fat and glycogen. Due to the large size of leg muscles, walking, running, and cycling are the most effective means of exercise to reduce body fat.

Medical nutrition therapy

Medical nutrition therapy (MNT) is a therapeutic approach to treating medical conditions and their associated symptoms via the use of a specifically tailored diet devised and monitored by a medical doctor, registered dietitian or professional nutritionist. The diet is based upon the patient's medical record, physical examination, functional examination and dietary history.

The role of MNT when administered by an MD or DO physician, dietitian or professional nutritionist is to reduce the risk of developing complications in pre-existing conditions such as type 2 diabetes as well as ameliorate the effects any existing conditions such as high cholesterol.

Pharmacotherapy of retrograde ejaculation

Pharmacotherapy of retrograde ejaculation represents various medications used to treat retrograde ejaculation. Retrograde ejaculation (RE) is defined as a substantial redirection of seminal fluid from the posterior urethra into the bladder (Pic. 1) and mainly caused by bladder neck dysfunction (Pic. 2). Men suffering from RE present with total, or sometimes partial, absence of semen, despite the sensation of an orgasm, after intercourse or masturbation. Current treatment methods are based on two different strategies. The first is pharmacologic intervention or surgical management in order to restore antegrade ejaculation by increasing bladder neck tone. The second is urinary sperm retrieval or electroejaculation; this aims to facilitate fertility by obtaining spermatozoa with invasive methods and then applying artificial reproductive technologies. 

The treatment depends on the cause. Medications may work for retrograde ejaculation but only in a few cases. Nevertheless, pharmacotherapy can be tried as a first-line treatment because it is simple, time-saving, cost-effective and non-invasive.

Currently, these medications are most commonly used:

  • tricyclic antidepressants (such as imipramine or amoxapine)
  • antihistamines (such as promethazine or diphenhydramine)
  • decongestants (such as pseudoephedrine)

These medications tighten the bladder neck muscles and prevent semen from going backwards, into the bladder. However, the medications do have many side effects and they have to be taken at least 1–2 hours prior to sexual intercourse.

Clinically, imipramine, a tricyclic antidepressant agent (TCA), is commonly used to treat RE due to a variety of causes. However, the overall success rate does not exceed 50%, and adverse effects are reported frequently.

Amoxapine, a tetracyclic antidepressant that is chemically distinct from TCAs, has been reported to result in far fewer adverse events than imipramine in patients treated for depression. Amoxapine also selectively blocks neuronal reuptake of norepinephrine and, to a lesser extent, serotonin, and thus upregulates peripheral sympathetic activity to contract the bladder neck; therefore, it also exerts actions that are potentially beneficial in the treatment of RE.

Around 40% of sufferers from retrograde ejaculation have found that use of pseudoephedrine (brands names include Sudafed) noticeably improves the quantity of ejaculate. People with erectile dysfunction and retrograde ejaculation (not uncommon in those with diabetes) are strongly advised to seek medical advice about the best 'dual' treatment methods available to them, i.e. combining pseudoephedrine or an alternative with an erectile dysfunction treatments such as sildenafil.

Surgical therapy of retrograde ejaculation

Surgical therapy of retrograde ejaculation represents surgical techniques used in the treatment of retrograde ejaculation. Retrograde ejaculation (RE) is defined as a substantial redirection of seminal fluid from the posterior urethra into the bladder (Pic. 1) and mainly caused by bladder neck dysfunction. Men suffering from RE present with total or sometimes partial absence of semen, despite the sensation of an orgasm, after intercourse or masturbation.

Current treatment methods are based on two different strategies. 

  1. The first is pharmacologic intervention or surgical management in order to restore antegrade ejaculation (ejaculation in the “healthy” direction) by increasing bladder neck tone. 
  2. The second is urinary sperm retrieval or electroejaculation; this aims to facilitate fertility by obtaining spermatozoa with invasive methods and then applying artificial reproductive technologies. 

The treatment of retrograde ejaculation is based on underlying aetiology. Anatomical causes, for instance, after prostate surgery, are rarely curable, and sperm harvesting from the urine should be considered if pregnancy is desired. Surgery rarely is the first option for retrograde ejaculation and the results have proven to be inconsistent. 

Sometimes, surgical treatment has been reported to be beneficial when medical treatment has failed. It usually involves surgical reconstruction of the neck of the urinary bladder and the adjoining part of the urethra. The goal is to restore the ability of the bladder neck to tighten during ejaculation and prevent the retrograde flow of semen.

Egg donation

Egg donation is the process by which a woman donates eggs for purposes of assisted reproduction or biomedical research. For assisted reproduction purposes, egg donation typically involves IVF technology, with the eggs being fertilized in the laboratory; more rarely, unfertilized eggs may be frozen and stored for later use. Egg donation is a third party reproduction as part of ART.

Egg donor may have several reasons for donate her eggs:

  • Unrelated donors to the recipients – they do it for altruistic and/or monetary reasons. The European Union limits any financial compensation for donors to at most $1500. In some countries, most notably Spain and Cyprus, this has limited donors to the poorest segments of society. In US, donors are paid regardless of how many egg she produces. In most countries (excluding the US and the UK), the law requires such type of donors to be anonymous.
  • Egg sharing – the woman decides to provide unused egg from her own IVF for another patient.
  • Designated donors – couple bring their friend or the donor specifically to help them.

Procedure

First step is choosing the egg donor by a recipient from the profiles on or clinic databases (or, in countries where donors are required to remain anonymous, they are chosen by the recipient's doctor based on recipient woman’s desired trait). This is due to the fact that all of the mentioned examinations are expensive and the agencies/clinics must first confirm that a match is possible or guaranteed before investing in the process. 

Each egg donor is first referred to a psychologist who will evaluate if she is mentally prepared to undertake and complete the donation process. These evaluations are necessary to ensure that the donor is fully prepared and capable of completing the donation cycle in safe and success manner. The donor is then required to undergo a thorough medical examination, including a pelvic exam, blood tests to check hormone levels and to test for infectious diseases, Rh factor, blood type, and drugs and an ultrasound to examine her ovaries, uterus and other pelvic organs. A family history of approximately the past three generations is also required, meaning that adoptees are usually not accepted because of the lack of past health knowledge. Genetic testing is also usually done on donors to ensure that they do not carry mutations (e.g., cystic fibrosis) that could harm the resulting children; however, not all clinics automatically perform such testing and thus recipients must clarify with their clinics whether such testing will be done. During the process, which usually takes several months, the donor must abstain from alcohol, sexual intercourse, cigarettes, and drugs, both prescription and non-prescription.

Once the screening is complete and a legal contract signed, the donor will begin the donation cycle, which typically takes between three and six weeks. An egg retrieval procedure comprises both the egg donor's cycle and the recipient's cycle. Birth control pills are administered during the first few weeks of the egg donation process to synchronize the donor's cycle with her recipient's, followed by a series of injections which halt the normal functioning of the donor's ovaries. These injections may be self-administered on a daily basis for a period of one to three weeks. Next, FSH is given to the donor to stimulate egg production and increases the number of mature eggs produced by the ovaries. Throughout the cycle the donor is monitored often by a physician using blood tests and ultrasound exams to determine the donor's reaction to the hormones and the progress of follicle growth.

Once the doctor decides the follicles are mature, the doctor will establish the date and time for the egg retrieval procedure. Approximately 36 hours before retrieval, the donor must administer one last injection of hCG to ensure that her eggs are ready to be harvested. The egg retrieval itself is a minimally invasive surgical procedure lasting 20-30 minutes, performed under sedation (but sometimes without any). A small ultrasound-guided needle is inserted through the vagina to aspirate the follicles in both ovaries, which extracts the eggs. After resting in a recovery room for an hour or two, the donor is released. Most donors resume regular activities by the next day.

Laws by state

The legal status and compensation of egg donation has several models across states with examples:

  • Totally illegal procedure (Italy, Germany, Austria, Costa Rica, Sunni Muslim countries, Bahrain, Egypt, Hong Kong, Lebanon, Lithuania, Maldives, Norway, Oman, Pakistan, Philippines, Qatar, Saudi Arabia, Syria, Tajikistan, Turkey, Yemen),
  • Legal, no compensation, anonymous donor (France),
  • Legal, no compensation, non-anonymous donor (Canada),
  • Legal, possible compensation, anonymous donor (Spain, Czech Republic, South Africa),
  • Legal, possible compensation, non-anonymous donor (the UK),
  • Legal, possible compensation, anonymous or non-anonymous (the US).

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ICSI

During ICSI just one sperm is injected directly into the egg cytoplasm using a micromanipulative apparatus that transforms imperfect hand movements into fine and precise movements of micromanipulation tools.

Intracytoplasmic Sperm Injection (ICSI) is an assisted reproductive technique (ART) initially developed by Dr. Gianpiero D. Palermo in 1993 to treat male infertility. It is most commonly used in conjunction with in vitro fertilization (IVF). Following IVF procedure, the physician places the fertilized egg into the female’s uterus for implantation. Sperm are obtained by the same methods as with IVF: either through masturbation, by using a collection condom, or by surgically removing sperm from a testicle through a small incision (MESA, TESE). The females are treated with fertility medications for approximately two weeks prior to oocyte retrieval to stimulate superovulation, where the ovaries produce multiple oocytes rather than the normal one oocyte. The oocytes are retrieved by either laparoscopy, or more commonly, transvaginal oocyte retrieval. In the latter procedure, the physician inserts a thin needle through the cervix, guided by a sonogram and pierces the vaginal wall and then the ovaries to extract several mature ova. Before the embryologist can inject the sperm into the oocyte, the sperm must be prepared by washing and exposing it to various chemicals to slow the sperm movement and prevent it from sticking to the injection plate. Also, the oocytes are treated with hyaluronidase to single out the oocyte ready for fertilization by the presence of the first polar body. Then, one prepared sperm is injected into an oocyte with a thin needle. Often, embryologists try to fertilize several eggs so they can implant more than one into the uterus and increase the chance of at least one successful pregnancy. This also allows them to save extra embryos, using cryopreservation, in case later IVF rounds are needed.

After the embryologist manually fertilizes the oocytes, they are incubated for sixteen to eighteen hours and develop into a pronucleate eggs (successfully fertilized eggs about to divide into an embryo). The egg then grows for one to five days in the laboratory before the physician places it in the female’s uterus for implantation.

The chance of fertilization increases dramatically with ICSI compared to simply mixing the oocytes and sperm in a Petri dish and waiting for fertilization to occur unaided (classical IVF procedure). Studies have shown that successful fertilizations occur 50% to 80% of the time. Since the introduction of ICSI, intrauterine insemination (IUI) has decreased in popularity by 80%.

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Postejaculatory urine sperm isolation - with ICSI

If a couple is experiencing infertility as a result of retrograde ejaculation and medications are not helping, the male's urine with ejaculate may be centrifuged and the isolated sperm injected directly into the woman's oocyte during IVF-ICSI procedure.

The  procedure includes adjustment of the osmolarity of the patient's urine by drinking water an urinary alkalization by an oral agent. The small amount of antegrade-produced ejaculate is collected in a plastic beaker, while the retrograde fraction of the ejaculate needs to be urinated immediately into a jar with culture medium containing human serum albumin to dilute the urine. Finally, the urine/medium mixture has to be centrifuged, resuspended and filtrated on the glass wool column where sperms are separated. When the sperm is isolate than it could be injected directly into the egg (which is maintained from woman by transvaginal oocyte retrieval). The following procedure is IVF-ICSI.

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Sperm donation

Sperm donation is the donation by a male (known as a sperm donor) of his sperm (known as donor sperm), principally for the purpose of inseminating a female who is not his sexual partner. Sperm donation is a form of third party reproduction including sperm donation, oocyte donation, embryo donation, surrogacy, or adoption. Number of births per donor sample will depend on the actual ART method used, the age and medical condition of the female bearing the child, and the quality of the embryos produced by fertilization. Donor sperm is more commonly used for artificial insemination (IUI or ICI) than for IVF treatments. This is because IVF treatments are usually required only when there is a problem with the female conceiving, or where there is a “male factor problem” involving the female's partner. Donor sperm is also used for IVF in surrogacy arrangements where an embryo may be created in an IVF procedure using donor sperm and this is then implanted in a surrogate. In a case where IVF treatments are employed using donor sperm, surplus embryos may be donated to other women or couples and used in embryo transfer procedures. 

On the other hand, insemination may also be achieved by a donor having sexual intercourse with a female for the sole purpose of initiating conception. This method is known as natural insemination.

The donation
Donor sperm and fertility treatments using donor sperm may be obtained at a sperm bank or fertility clinic. Here, the recipient may select donor sperm on the basis of the donor's characteristics, e.g. looks, personality, academic ability, race, and many other factors. Sperm banks or clinics may be subject to state or professional regulations, including restrictions on donor anonymity and the number of offspring that may be produced, and there may be other legal protections of the rights and responsibilities of both recipient and donor. Some sperm banks, either by choice or regulation, limit the amount of information available to potential recipients; a desire to obtain more information on donors is one reason why recipients may choose to use a known donor and/or private donation.

A sperm donor will usually donate sperm to a sperm bank under a contract, which typically specifies the period during which the donor will be required to produce sperm, which generally ranges from 6–24 months depending on the number of pregnancies which the sperm bank intends to produce from the donor. Donors may or may not be paid for their samples, according to local laws and agreed arrangements. Even in unpaid arrangements, expenses are often reimbursed. Depending on local law and on private arrangements, men may donate anonymously or agree to provide identifying information to their offspring in the future. Private donations facilitated by an agency often use a "directed" donor, when a male directs that his sperm is to be used by a specific person. Non-anonymous donors are also called known donors, open donors or identity disclosure donors.

Donor selection
A sperm donate must generally meet specific requirements regarding age (most often up to 40) and medical history. Potential donors are typically screened for genetic diseases, chromosomal abnormalities and sexually transmitted infections that may be transmitted through sperm. The donor's sperm must also withstand the freezing and thawing process necessary to store and quarantine the sperm. Samples are stored for at least 6 months after which the donor will be re-tested for sexually transmitted infections. This is to ensure no new infections have been acquired or have developed during the period of donation. If the result is negative, the sperm samples can be released from quarantine and used in treatments.

Screening includes:

  • Taking a medical history of the donor, his children, siblings, parents, and grandparents etc. for three to four generations back. This is often done in conjunction with the patient’s family doctor.
  • HIV risk assessment interview, asking about sexual activity and any past drug use.
  • Blood tests and urine tests for infectious diseases, such as: HIV-1/2, HTLV-1/2, Hepatitis B and C, Syphilis, Gonorrhea, Chlamydia, Cytomegalovirus (CMV), not all clinics test for this.
  • Blood and urine tests for blood typing and general health indicators: ABO/Rh typing, CBC, liver panel and urinalysis
  • Complete physical examination including careful examination of the penis, scrotum and testicles.
  • Genetic testing for carrier traits, for example: Cystic Fibrosis, Sickle-cell disease, Thalassemia, other hemoglobin-related blood disorders.
  • General health
  • Semen analysis for: sperm count, morphology, motility, acrosome activity may also be tested

Preparing the samples
A sperm donor is usually advised not to ejaculate for two to three days before providing the sample, to increase sperm count and to maximize the conception rate. A sperm donor produces and collects sperm by masturbation or during sexual intercourse with the use of a collection condom.

Sperm banks and clinics usually "wash" the sperm sample to extract sperm from the rest of the material in the semen. A cryoprotectant semen extender is added if the sperm is to be placed in frozen storage in liquid nitrogen, and the sample is then frozen in a number of vials or straws. One sample will be divided into 1-20 vials or straws depending on the quantity of the ejaculate and whether the sample is washed or unwashed. Following the necessary quarantine period, the samples are thawed and used to inseminate women through artificial insemination or other ART treatments. Unwashed samples are used for ICI treatments, and washed samples are used in IUI and IVF procedures.

Anonymity
Anonymous sperm donation occurs where the child and/or receiving couple will never learn the identity of the donor, and non-anonymous when they will. Non-anonymous sperm donors are, to a substantially higher degree, driven by altruistic motives for their donations.

Even with anonymous donation, some information about the donor may be released to the female/couple at the time of treatment. Limited donor information includes height, weight, eye, skin and hair color. In Sweden, this is all the information a receiver gets. In the US, on the other hand, additional information may be given, such as a comprehensive biography and sound/video samples.

Information made available by a sperm bank will usually include the race, height, weight, blood group, health, and eye color of the donor. Sometimes information about his age, family history and educational achievements will also be given.

Different factors motivate individuals to seek sperm from outside their home state. For example, some jurisdictions do not allow unmarried women to receive donor sperm. Jurisdictional regulatory choices as well as cultural factors that discourage sperm donation have also led to international fertility tourism and sperm markets.

Legal aspects
A sperm donor is generally not intended to be the legal or de jure father of a child produced from his sperm. Depending on the jurisdiction and its laws, he may or may not later be eligible to seek parental rights or be held responsible for parental obligations. Generally, a male who provides sperm as a sperm donor gives up all legal and other rights over the biological children produced from his sperm. However, in private arrangements, some degree of co-parenting may be agreed, although the enforceability of those agreements varies by jurisdiction.

Laws prohibits sperm donation in several countries: Algeria, Bahrain, Costa Rica, Egypt, Hong Kong, Jordan, Lebanon, Lithuania, Libya, Maldives, Oman, Pakistan, Philippines, Qatar, Saudi Arabia, Syria, Tajikistan, Tunisia, Turkey, UnitedArab Emirates, and Yemen. 

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Standard IVF

In vitro fertilization (IVF) is a process by which an egg is fertilised by sperm outside the body: in vitro . The process involves monitoring and stimulating a woman's ovulatory process, removing an ovum or ova (egg or eggs) from the woman's ovaries and letting sperm fertilise them in a liquid in a laboratory. The fertilised egg (zygote) is cultured for 2–6 days in a growth medium and is then implanted in the same or another woman's uterus, with the intention of establishing a successful pregnancy.

IVF techniques can be used in different types of situations. It is a technique of assisted reproductive technology for treatment of infertility. IVF techniques are also employed in gestational surrogacy, in which case the fertilised egg is implanted into a surrogate's uterus, and the resulting child is genetically unrelated to the surrogate. In some situations, donated eggs or sperms may be used. Some countries ban or otherwise regulate the availability of IVF treatment, giving raise to fertility tourism. Restrictions on availability of IVF include to single females, to lesbians and to surrogacy arrangements. Due to the costs of the procedure, IVF is mostly attempted only after less expensive options have failed.

The first successful birth of a "test tube baby", Louise Brown, occurred in 1978. Louise Brown was born as a result of natural cycle IVF where no stimulation was made. Robert G. Edwards, the physiologist who developed the treatment, was awarded the Nobel Prize in Physiology or Medicine in 2010. With egg donation and IVF, women who are past their reproductive years or menopause can still become pregnant. Adriana Iliescu held the record as the oldest woman to give birth using IVF and donated egg, when she gave birth in 2004 at the age of 66, a record passed in 2006.

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How can Ejaculatory disorders affect fertility

Ejaculatory dysfunction is very common and stressful thing for men. It is a significant cause of male subfertility, posing distinct reproductive challenges for couples attempting to conceive. While delayed ejaculation and premature ejaculation are sources of sexual dissatisfaction for men and their partners, patients with these disorders could retain fertile in most cases. 

Men with anejaculation or retrograde ejaculation are unable to deliver sperm into the female genital tract and are therefore rendered subfertile. For them, there are techniques of assisted reproduction.

Mechanism_of_Ejaculation
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