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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Turner syndrome treatments

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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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Embryo donation

Embryo donation is defined as the giving of embryo or both gametes to another person or couple unable to produce their own genetic embryo for implantation. Other reason is to donate embryos for research. Where it is given for the purpose of implantation, the donation is followed by the placement of those embryos into the recipient woman's uterus to facilitate pregnancy and childbirth in the recipient. 

Donated embryo origin

Unused embryos from a successful IVF of one couple may be given (depending on the local law) to other couples or women for transfer with the goal of producing a successful pregnancy. Embryos for embryo donation may also be created specifically for embryo transfer using donor eggs and donor sperm. 

Anonymity of the donor

Embryo donation is most often handled on an anonymous basis (donor and recipient parties are not known to each other), or on an open basis (parties' identities are shared and the families agree to a relationship). Occasionally, a "semi-open" arrangement is used in which the parties know family and other information about each other, but their real names and locating information are withheld, in order to provide a layer of privacy protection.

Process

Both donor and recipient have to be screened to ensure success the embryo donation treatment.

Embryo donor screening includes:

  • Optimal age of the donor is 19 – 33 years,
  • Genetic screening for family history, hereditary diseases and normal karyotype,
  • Genetic testing for blood type, cystic fibrosis and hemoglobinopathies,
  • Serologic al examination on hepatitis B and C, syphilis, HIV and re-screening before the embryos are thawed and transferred,
  • Psychological and mental screening.

Embryo recipient screening includes:

  • Ultrasound examination of uterus lining,
  • Cytology examination not older than 12 months, confirmation from a gynecologist that pregnancy is not a contraindicated, and mammographic examination (women older than 45 years),
  • Serologic al examination on HIV, hepatitis B and C, syphilis,
  • Once all parties agree, the embryo is transferred to the adoptive mother's clinic for an embryo transfer.

Embryo donation vs. embryo adoption

Some writers use the term "embryo donation" to refer strictly to anonymous embryo donation, and "embryo adoption" to refer to the open process. Others use the terms synonymously because regardless of whether the arrangement is open or anonymous, the donation of embryos and a clinical assisted reproduction procedure is involved, and the recipient couple is preparing to raise a child not genetically related to them. Lawyers who assist couples who are trying to acquire an embryo state the term "embryo adoption" is a misnomer because the transfer of an embryo is handled as property transfer. Abortion rights advocates, advocates of embryonic stem cell research, and members of the fertility industry object to referring to the transfer as an "adoption" because they feel it gives an embryo the same status as a child. Most doctors describe the process as "embryo donation".

The resulting child is considered the child of the woman who carries it and gives birth, and not the child of the donor. This is the same principle as is followed in egg donation or sperm donation. Most often, the embryos are donated after the woman for whom they were originally created has successfully carried one or more pregnancies to term.

Laws by state

In most states, the birth mother becomes a child’s legal mother and her husband is a child’s legal father, if she has any. 

Embryo donation is performed in these countries: Canada, UK, France, Spain, Italy, Australia, Belgium, India, Greece, Singapore, Argentine, Colombia, the Czech Republic, Japan, the Netherlands, Uruguay, Romania, Portugal, Venezuela, Hong Kong, New Zealand, Russia, Singapore, and Finland. In the US, all 50 states and the District of Columbia permit living embryo adoption and implantation.   

In these countries, embryo donation is illegal: Algeria, Austria, Bahrain, China, Denmark, Germany, Egypt, Israel, Italy, Latvia, Lithuania, Norway, Pakistan, Philippines, Qatar, Oman, Saudi Arabia, Slovenia, Sweden, Switzerland, Syria, Taiwan, Tajikistan, Tunisia, Turkey, United Arab Emirates and Yemen.

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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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Preimplantation genetic screening

In the last 30 years, genetic testing techniques have been developed to identify chromosomally normal embryos in vitro, thereby potentially increasing the proportion of successful cycles with elective single-embryo transfer, and minimizing twin-pregnancy complications and miscarriages. This testing is termed "pre-implantation genetic screening" (PGS), in contrast to pre-implantation genetic diagnosis PGD), in which testing is performed for specific genetic defects. 

Today, PGS technologies have evolved to include screening of all 24 chromosomes (22 pairs of autosomes and the 2 sex chromosomes). Ongoing pregnancy rates of about 60% following single embryo transfer have been described in couples with a maternal age of 38 years whose embryos have undergone PGS. It has not, however, been definitively established that the cumulative delivery rates are better with PGS, although it has been argued that the reduction in miscarriage rates and maternal and neonatal complications due to multiple pregnancies justifies the expense of this technology.

Trends toward delayed childbearing have resulted in an increasing number of women of advanced maternal age seeking to become pregnant and in a consequent increase in demand for assisted reproductive technology, most commonly in-vitro fertilization (IVF). In such women, the proportion of aneuploid embryos can exceed 60%, with a risk of miscarriage of about 40%, potentially resulting in significant emotional and financial hardship for affected couples.

Indications for PGS

Commonly quoted indications for PGS include advanced maternal age, repeated implantation failure, recurrent miscarriage, severe male factor infertility, or subfertility (those who experience unrecognized embryonic losses and who are labelled clinically as infertile). It should be noted that the chances of selecting an euploid embryo mainly depend of the number of embryos produced during the procedure. When it is suspected that the couple has a major chromosomal risk due to advanced maternal age or severe male factors, it is mandatory to inform them of the low chance of achieving a pregnancy with the PGS procedure, unless the couple produces many embryos that provide one or two euploid embryos apt for transfer.

  • Advanced Maternal Age

Women at an advanced age have a greater chance of having aneuploid pregnancies because they have increased rates of producing aneuploid oocytes. Oocytes are always the same age as the woman. However, in males, sperm are produced every 65-75 days. Therefore, it might be said that sperm are not the same age as the male. The prolonged arrest of oocytes at meiotic prophase I mainly contributes to aneuploidy due to the decline in competence of the cytoplasm of the oocyte. The number and distribution of chiasmata during prophase I as the weak centromeric cohesion may be the main factor that predisposes aneuploidy that is inherent to age. In fact, the principal cause of oocyte aneuploidy is the precocious separation of sister chromatids rather than classic non-disjunction. In the male, the expected sperm aneuploidy rate is between 0.5 and 1% because the sperm is not the age of the male, but if the sperm is not ejaculated for prolonged periods, it could have a high rate of DNA fragmentation, which is also responsible for abnormal fertilization. Competent oocytes from young women can repair the DNA fragmentation of the sperm, but the oocytes from older women cannot. Therefore, women of advanced age have higher probabilities of having abnormal pregnancies that might end in miscarriage or in a malformed newborn. Most of these embryos are lost during pre or post implantation stages, while a minority come to term. That is why the possibility of miscarriage also increases with the age of the woman (Tab. 1).

  • Recurrent Pregnancy Loss (RPL)

Usually, RPL is defined as two or more consecutive pregnancies lost before 20 weeks of gestation. Different cytogenetic studies of miscarriages in the first trimester of pregnancy show that aneuploidy rates varied between 50% and 80%. Additionally, it has been documented that couples with RPL produce more aneuploid embryos than those who have not had RPL (Pellicer et al., 1999). According to some authors, PGS does not improve the rate of pregnancy in RPL, but increases the chance of birth at term (Platteau et al., 2005).

  • Recurrent IVF Failure (RIF)

RIF is usually defined as the failure of three or more IVF attempts with good quality embryo transfer. Some authors argue that these couples produce more embryos with aneuploidies. However, there is no evidence that PGS improves the rate of pregnancy or live IVF births.

  • Severe Male Factors

As mentioned above, the rate of aneuploidy in spermatozoa from fertile males with a normal spermiogram is much lower than that observed in oocytes, and aneuploidy also does not increase with age in men. On the other hand, sperm aneuploidies increase with the severity of OAT. These findings put in evidence the importance of the genetic risk assessment before the ICSI procedure to predict the chance of success. Now, with the possibility of PGS/PGD and lower costs, FISH is no longer used to assess sperm.

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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 Turner syndrome affect fertility

Women with Turner syndrome are almost universally infertile since TS is characterized by primary amenorrhoea, premature ovarian failure and streak gonads. Usually estrogen replacement therapy is used to spur growth of secondary sexual characteristics at the time when puberty should onset. While very few women with Turner syndrome menstruate spontaneously, estrogen therapy requires a regular shedding of the uterine lining ("withdrawal bleeding") to prevent its overgrowth. Withdrawal bleeding can be induced monthly, like menstruation, or less often, usually every three months, if the patient desires. Estrogen therapy does not make a woman with nonfunctional ovaries fertile, but it plays an important role in assisted reproduction; the health of the uterus must be maintained with estrogen if an eligible woman with Turner syndrome wishes to use IVF (using donated oocytes). While some women with Turner syndrome have successfully become pregnant and carried their pregnancies to term, this is very rare and is generally limited to those women whose karyotypes are not 45,X. Even when such pregnancies do occur, there is a higher than average risk of miscarriage or birth defects, including Turner syndrome or Down syndrome. As more women with Turner syndrome complete pregnancy thanks to modern techniques to treat infertility (donor egg can be used to create an embryo, which is carried by the Turner syndrome woman), it has to be noted that pregnancy may be a risk of cardiovascular complications for the mother. Indeed, several studies had suggested an increased risk for aortic dissection in pregnancy. Three deaths have even been reported. The influence of estrogen has been examined but remains unclear. It seems that the high risk of aortic dissection during pregnancy in women with Turner syndrome may be due to the increased hemodynamic load rather than the high estrogen rate. Of course these findings are important and need to be remembered while following a pregnant patient with Turner syndrome.

Neck Turner
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