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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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.

Stop smoking

Stop smoking is a process of discontinuing tobacco smoking. Cigarette smoking remains the leading preventable cause of death and disease in the developed world, and increasing the number of smokers successfully quitting is one of the most effective measures available to improve population health. Stop smoking isn’t easy but with the right tools and support quitting smoking is possible and will be one of the most rewarding achievements of your life.

Smoking is a practice in which a substance is burned and the resulting smoke breathed in to be tasted and absorbed into the bloodstream. Most commonly the substance is the dried leaves of the tobacco plant which contains nicotine, which is addictive, making the process of quitting often very prolonged and difficult.

Nicotine binds to nicotinic receptors in the brain that, in turn, cause an increase indopamine. Dopamine is the major chemical that stimulates reward centers in the brain. The brain recruits an opposing force to dampen the effects of nicotine and this causes tolerance (the reduction in the effect of nicotine). The onset of this opposing force and the fact that the brain becomes used to and dependent on nicotine to function normally is known as physical dependence. When nicotine intake is decreased, the brain's opposing force is now unopposed and this causes withdrawal symptoms.

Ways how stop smoking

  • Unassisted
Only 6% on average will successfully stop smoking their first try. Summoning up the willpower to make that decision permanent is key to succeeding in the long run.´

There is no significant difference in quit rates between smokers who quit by gradual reduction or abrupt cessation as measured by abstinence from smoking of at least six months from the quit day, suggesting that people who want to quit can choose between these two methods.

Gradual reduction involves slowly reducing one's daily intake of nicotine. This can theoretically be accomplished through repeated changes to cigarettes with lower levels of nicotine, by gradually reducing the number of cigarettes smoked each day, or by smoking only a fraction of a cigarette on each occasion.

  • Nicotine replacement therapy
Nicotine replacement therapies including patches, lozenges, gum, inhalators, mouth spray, and mouth strips give your body some nicotine without all the harmful chemicals in cigarette smoke. Nicotine replacement therapy should be used for at least 8 weeks.

  • Pharmacotherapy
Varenicline Tartate (Champix)- is a non-nicotine medication designed to block the nicotine receptors in the brain. People who want to quit will need to get a prescription from their doctor to use Champix. The treatment course is 12 weeks.
Bupropion (Zyban)- is a non-nicotine medication designed to work on the reward pathways in the brain to minimise nicotine withdrawal symptoms. People who want to quit will need to get a prescription from their doctor to use Zyban. The treatment course is 9 weeks.

  • Psychosocial approaches
Group or individual psychological support can help people who want to quit. This form of counselling can be effective alone; combining it with medication is more effective, and the number of sessions of support with medication correlates with effectiveness. The counselling styles that have been effective in smoking cessation activities include motivational interviewing, cognitive behavioural therapy and Acceptance and Commitment Therapy.

People quit in different ways, so it is important to think about what way would suit you best. Some people prefer to cut down their smoking before quitting altogether. Others like to set a quit date and abruptly stop. Quit smoking medication and nicotine replacement therapy can be used to help you cut down and ease into quitting.

Antithrombotic therapy

Antithrombotic therapy is summarily the administration of drugs that reduce the formation of thrombi (blood clots). These drugs are widely used both for therapeutic and preventive purposes. 

Antithrombotics are commonly divided into three basic categories (Antiplatelet therapy, Anticoagulation therapy and Thrombolytics).

1. Antiplatelet therapy

Antiplatelet drugs inhibit the aggregation of blood platelets and thus the formation of thrombi, a process known as thrombosis. They play a major role in preventing the formation of arterial thrombosis where anticoagulation therapy is less effective. Therefore, they are widely used in the prevention of various cardiovascular and cerebrovascular diseases (so-called primary prevention), and in patients who have suffered these diseases in the past, are therefore in increased risk of experiencing them again (secondary prevention) and have been treated with invasive intravascular techniques. These conditions include myocardial infarction (heart attack), coronary intervention, STENT implantation (insertion of a plastic or metal tube into a blood vessel, to preserve its patency) stroke or advanced atherosclerosis (narrowing of arteries due to deposition of lipid-rich substances in the arterial wall). 

Antiplatelet therapy (most commonly Aspirin, see below) is also used as a part of the treatment of Antiphospholipid syndrome. Antiphospholipid syndrome is an autoimmune disease, in which "antiphospholipid antibodies” react against proteins that bind to anionic phospholipids on plasma membranes. Antiphospholipid syndrome causes thrombosis in both arteries and veins, and is associated with various adverse pregnancy outcomes, such as such as miscarriage, stillbirth, preterm delivery, and severe preeclampsia (combination of oedemas, high blood pressure, and presence of protein in the urine during pregnancy, with potentially life-threatening complications). Antiphospholipid syndrome often requires antithrombotic therapy with both antiplatelet and anticoagulant medications to improve the outcomes of the pregnancy.

The most commonly used antiplatelet medications include:

  • Cyclooxygenase inhibitors - most notably acetylsalicylic acid, known as Aspirin.
  • ADP receptor antagonists – Clopidogrel (Plavix), Prasugrel (Effient), and Ticagrelor (Brilinta).
  • Glycoprotein IIB/IIIA inhibitors – Abciximab, Tirofiban and Eptifibatide, used intravenously only.

In high-risk patients, so-called dual antiplatelet therapy is used, which consist of simultaneous administration of Aspirin and one of ADP receptor antagonists, most commonly Clopidogrel.

2. Anticoagulation therapy

Anticoagulants are drugs used to prevent mainly venous thrombosis, where the process is usually initiated by abnormal activation of the coagulation cascade (the process of forming a blood clot by a chain reaction of a number of blood proteins). The formation of thrombi inside veins is also associated with the risk of embolism – dislocation of the thrombus and its migration into the pulmonary circulation, causing a condition known as pulmonary embolism (Pic. 1). These conditions characterised by the presence of venous thrombi are therefore know sumarily as thromboembolic disease. The main treatment goal for anticoagulation therapy is to reduce the risk of thromboembolic disease in patients with atrial fibrillation (AF), mechanical heart valves, deep vein thrombosis (DVT) and pulmonary embolism, while at the same time minimising the risk of bleeding as a result of toxicity.

Anticoagulants can be administered either orally (oral anticoagulants), or by subcutaneous or intravenous injections (heparins). Oral anticoagulants are represented by the drug warfarin (Pic. 2), and a group known as novel oral anticoagulants (NOACs), including dabigatran, apixaban and rivaroxaban. Heparins are administered parenterally (by injection) and are classified based on their molecular weight. The most commonly used group are so-called low-molecular weight heparins (LMWH, Pic. 3). 

Pregnant women are generally in an increased risk of thrombosis due to the pro-thrombogenic effect of pregnancy. Some women with an added risk of thrombosis (with a history of DVT, pulmonary embolism, with mechanical heart valves or with genetic predispositions for thromboembolic disease) may need anticoagulation therapy during the whole course of pregnancy to ensure the safety of the fetus. The main issue with anticoagulation in pregnancy is that warfarin, the most commonly used anticoagulant in chronic administration, is known to have teratogenic effects on the fetus if administered in early pregnancy. There is no consensus opinion on the correct anticoagulation regimen during pregnancy. Treatment is tailored to the particular individual based on their risk of complications. Pregnant women in need of anticoagulation therapy during pregnancy are, however, usually converted from warfarin to heparin or LMWH for the duration of the pregnancy.

3. Thrombolytics

Thrombolytic agents act by actively dissolving thrombi that have already been formed. They are most commonly used in the treatment of stroke and pulmonary embolism. The most commonly used thrombolytic drug is the analog of tissue plasminogen activator (TPA).

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.

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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Intralipid infusion therapy

Intralipid prior to an IVF procedure , dramatically increases pregnancy success rates while reducing the risk of miscarriage. Plays a role in helping a newly implanted embryo attach to the mother’s uterus and begin to thrive.It consists of 20% Soybean Oil, 1.2% Egg Yolk Phospholipids, 2.25% Glycerin, and Water . Given as an intravenous infusion it bypasses the stomach and goes directly into the bloodstream to supply the body with several essential fatty acids. These are substances required for many biological functions, including reproduction – but they can’t be made by the body. As such they must be obtained via food, supplements, or in this case the intravenous infusion.

Intralipid infusion therapy is a sterile fat emulsion containing soy oil, chicken egg yolk, glycerine and water.  The infusion is in liquid form and administered intravenously.  It is a non invasive procedure carried out in clinic as part of a treatment cycle.

In the case of miscarriages, repeated implantation failure and  elevated NK levels intralipids might help but not will have to.

http://www.midlandfertility.com/recurrent-miscarriage-tests/intralipid-infusion/

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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 Antiphospholipid syndrome affect fertility

Anti-phospholipid syndrome is thought to be a major cause of early pregnancy loss. This condition is characterized by the presence of anti-phospholipid antibody. In pregnant women affected by APS, miscarriage can occur prior to 20 week of gestation, while pre-eclampsia is reported to occur after that time. Placental infarctions, early deliveries and stillbirth are also reported in women with APS. In some cases, APS seems to be the leading cause of mental and/or development retardation in the newborn, due to an aPL (antiphospholipid antibodies)-induced inhibition of trophoblast differentiation. The antiphospholipid syndrome responsible for most of the miscarriages in later trimesters seen in concomitant systemic lupus erythematosus and pregnancy.

Thrombotic microangiopathy
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