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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Bicornuate uterus 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).

See full description of Egg donation

Elective single embryo transfer

The technique of selecting only one embryo to transfer to the woman is called elective-Single Embryo Transfer (e-SET) or, when embryos are at the blastocyst stage, it can also be called elective single blastocyst transfer (eSBT). It significantly lowers the risk of multiple pregnancies, compared with e.g. double embryo transfer (DET) or double blastocyst transfer (2BT), with a twinning rate of approximately 3.5% in sET compared with approximately 38% in DET, or 2% in eSBT compared with approximately 25% in 2BT. At the same time, pregnancy rates is not significantly less with eSBT than with 2BT. That is, the cumulative live birth rate associated with single fresh embryo transfer followed by a single frozen and thawed embryo transfer is comparable with that after one cycle of double fresh embryo transfer.

Given that the transfer of multiple embryos increases the risk of a multiple gestation, many have suggested a move towards elective single embryo transfer (eSET), although this recommendation has been focused mainly on women less than age 36. In a fresh IVF cycle, single-embryo transfer (SET) is associated with a lower rate of multiple pregnancies than other principles of embryo transfer. For this reason, SET became more popular in the past decade and had a good perinatal outcome in the US, in the Nordic countries, and even in Asia in recent years. Several randomized controlled trials in Europe have demonstrated that eSET significantly diminishes twin gestations and yields comparable live birth rates in good prognosis patients (Graph 1).

A handful of European studies have also addressed the role of eSET in the advanced maternal age population. One study found that eSET could be safely applied to patients aged 36–39, while dramatically decreasing the multiple gestation rate (MGR) and achieving similar pregnancy rates (PRs). Another study found that eSET could be offered to women younger than 38 in the first three IVF treatment cycles without compromising PR, although the mean patient age in this study was 32.5 years.

While these studies analyzing eSET have focused primarily on day 3 embryo transfer, blastocyst transfer (BT) has also emerged as a potential approach to reducing MGR as generally fewer embryos are transferred. Several studies have shown superior outcomes with BT compared to cleavage stage embryo transfer (see Tab. 1). The superior implantation rate seen with BT has mainly been attributed to better embryo selection.

Selection of the best embryo for transfer is crucial for the eSET. During the past 15 years, various approaches were suggested, including morphological classification, proteomic and metabolomic investigations and time lapse follow-up. The increasing incidence of aneuploidy with advanced maternal age requires a reliable diagnostic method for chromosome aneuploidies, and recent reports indicate that none of the non-invasive approaches are reliable enough for this purpose. Therefore, embryo biopsy, preferably at the blastocyst stage and accompanied by comprehensive chromosome screening may be advised in some patients with higher risk of aneuploidy.

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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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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. 

See full description of Sperm donation

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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Surrogacy

Surrogacy describes an alternate means of conception for individuals who are unable to conceive a child naturally. In surrogacy, one woman (surrogate mother) carries a child for another person/s (commissioning person/couple), based on an agreement before conception requiring the child to be handed over to the commissioning person/couple following birth.

Traditional surrogacy is defined as a woman who agrees to carry a pregnancy using her own oocytes but the sperm of another couple and relinquish the child to this couple upon delivery. The surrogate is naturally or artificially inseminated via IUI, IVF or home insemination. With this method, the resulting child is genetically related to intended father and genetically related to the surrogate mother.

Gestational surrogacy, by contrast, involves a couple who undergoes IVF with their genetic gametes and then places the resultant embryo in another woman’s uterus, the gestational carrier, who will carry the pregnancy and relinquish the child to this couple upon delivery. The resulting child is genetically unrelated to the surrogate. There are several sub-types of gestational surrogacy as noted below.

  • Using the intended mother's egg - a surrogate is implanted with an embryo created by IVF, using intended father's sperm and intended mother's eggs.
  • Using an egg donor - a surrogate is implanted with an embryo created by IVF, using intended father's sperm and a donor egg where the donor is not the surrogate. The resulting child is genetically related to intended father and genetically unrelated to the surrogate.
  • Using a sperm donor - a surrogate is implanted with an embryo created by IVF, using intended mother's egg and donor sperm. The resulting child is genetically related to intended mother and genetically unrelated to the surrogate.
  • Using an embryo donor - a donor embryo is implanted in a surrogate; such embryos may be available when others undergoing IVF have embryos left over, which they opt to donate to others. The resulting child is genetically unrelated to the intended parent(s) and genetically unrelated to the surrogate.

Currently, the use of gestational carriers is far more common than that of surrogates.

The process 

A surrogacy contract is a contract no different to any other contract as it essentially relates to the agreement or promise made by both parties: contract law is primarily concerned with agreements that involve one party, or each party, giving an undertaking or promise to the other party. The rights and duties of the surrogate stem from two basic promises that she makes to the commissioning couple. First, she promises to be treated with the commissioning couple's genetic material (partial/full surrogacy) and carry the child to term. The surrogate will also give an assurance that she will attend regular prenatal appointments so as to ensure the health and safety of the foetus.

Secondly, the surrogate will promise to surrender all rights in the child to the commissioning couple. This latter promise may become complicated if the surrogate is married, as the law presumes that a child born to a married woman is the child of the woman and her husband. However, this presumption is rebuttable and thus, the commissioning couple should from the outset, make it a term of the contract that the surrogate and her husband explicitly agree to make no claim to the resulting child; without this statement, the intention of the parties may be undercut. Such a provision would help reduce emotional strain and the probability of litigation, and would avoid harming the child by involving it in custody proceedings.

A surrogacy arrangement based on contractual intention should not be designed to commodify offspring. Surrogacy arrangements do not deal with fungibles and must not encourage a system where children are treated as goods that may be contracted in and out of. While the notion of surrogacy could understandably figure centrally in the arena of family law, when examining the matrix of relationships embraced by surrogacy, one may see that surrogacy also has a basis in contract law. As with all contracts, they are designed to protect the interests of both parties as well as to bring to fruition, the express and implied terms of the contract. This perspective derives from the basic agreement made between the surrogate and the commissioning couple; the surrogate agrees to carry the foetus to term, for the benefit of the commissioning person/s and, the latter agree to re-compensate the surrogate for her time and expense in carrying out said procedure, of which, would not be possible without her agreement.

Surrogacy arrangement

There are 2 types of surrogacy arrangement:

  • Altruistic (non-commercial),
  • Commercial – there is a payment, reward or any material benefit for surrogate.

Legal aspects

If the jurisdiction specifically prohibits surrogacy, however, and finds out about the arrangement, there may be financial and legal consequences for the parties involved. Some jurisdictions specifically prohibit only commercial and not altruistic surrogacy. Even jurisdictions that do not prohibit surrogacy may rule that surrogacy contracts (commercial, altruistic, or both) are void. If the contract is either prohibited or void, then there is no recourse if one party to the agreement has a change of heart: If a surrogate changes her mind and decides to keep the child, the intended mother has no claim to the child even if it is her genetic offspring, and the couple cannot get back any money they may have paid or reimbursed to the surrogate; if the intended parents change their mind and do not want the child after all, the surrogate cannot get any reimbursement for expenses, or any promised payment, and she will be left with legal custody of the child.

Jurisdictions that permit surrogacy sometimes offer a way for the intended mother, especially if she is also the genetic mother, to be recognized as the legal mother without going through the process of abandonment and adoption.

Often this is via a birth order in which a court rules on the legal parentage of a child. These orders usually require the consent of all parties involved, sometimes including even the husband of a married gestational surrogate. Most jurisdictions provide for only a post-birth order, often out of an unwillingness to force the surrogate mother to give up parental rights if she changes her mind after the birth.

A few jurisdictions do provide for pre-birth orders, generally in only those cases when the surrogate mother is not genetically related to the expected child. Some jurisdictions impose other requirements in order to issue birth orders, for example, that the intended parents be heterosexual and married to one another. Jurisdictions that provide for pre-birth orders are also more likely to provide for some kind of enforcement of surrogacy contracts.

Additionally, the rights of the surrogate or gestational carrier to not relinquish the infant following deliver are not well described.

Parentage order

A parentage order is a court order that transfers parentage from the birth parent/s to the intended parent/s - as part of the surrogacy arrangement. This means the birth mother and her partner (if she has one) no longer have a legal parental relationship with the child and the intended parents become the child’s legal parents. A prebirth form of parentage order could be used.

Surrogacy laws by state

Surrogacy is completely prohibited in Finland, France, China, Iceland, Italy, Japan, Pakistan, Saudi Arabia, Serbia, Spain and Switzerland. 

Countries where a commercial surrogacy is legal and a woman could be paid to carry another's child through IVF and embryo transfer included Georgia, Russia, Thailand, Ukraine and a few US states.

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How can Bicornuate uterus affect fertility

Previously, a bicornuate uterus was thought to be associated with infertility, but recent studies have not confirmed such an association. Pregnancies in a bicornuate uterus are usually considered high risk and require extra monitoring because of association with poor reproduction potential.

A bicornuate uterus is associated with increased adverse reproductive outcomes, such as: 
  • Recurrent pregnancy loss
  • Preterm birth: the rate of preterm delivery is 15 to 25%. A pregnancy may not reach full term in a bicornuate uterus when the baby begins to grow in either of the uterine horns. A short cervical length seems to be a good predictor of preterm delivery in women with a bicornuate uterus.
  • Malpresentation (breech birth or transverse presentation): a breech presentation occurs in 40-50% of pregnancies with a partial bicornuate uterus and not at all (0%) in a complete bicornuate uterus.
  • Deformity: Offspring of mothers with a bicornuate uterus are at high risk for deformities and disruptions and malformations.
Pic.1: Bicornuate uterus
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