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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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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Intrauterine insemination

Intrauterine insemination (IUI) as a type of artificial insemination involves the placement of sperm directly into the uterus at the time of ovulation, either in a natural menstrual cycle or following ovarian stimulation. The process allows the concentration of sperm in a small volume of culture media and then the concentrated sperm is placed into the uterus through a transcervical catheter. IUI has the advantages of being less invasive and more affordable than other assisted reproduction techniques such as IVF. IUI theoretically allows a relatively higher number of motile sperm to reach the oocyte. The rationale for washing sperm is to remove prostaglandins, infectious agents, and antigenic proteins as well as to remove immotile spermatozoa, leucocytes, and immature germ cells. 

IUI is a more efficient method of artificial insemination. Sperm is occasionally inserted twice within a “treatment cycle“. A double intrauterine insemination theoretically increases pregnancy rates by decreasing the risk of missing the fertile window during ovulation. However, a randomized trial of insemination after ovarian hyperstimulation found no difference in live birth rate between single and double intrauterine insemination.

Unlike intracervical insemination, intrauterine insemination normally requires a medical practitioner to perform the procedure (see Tab. 1). A female under 30 years of age has optimal chances with IUI; for the man, a total motile sperm count of more than 5 million per ml is optimal. In practice, donor sperm will satisfy these criteria. A promising cycle is one that offers two follicles measuring more than 16 mm, and estrogen of more than 500 pg/mL on the day of hCG administration. A short period of ejaculatory abstinence before intrauterine insemination is associated with higher pregnancy rates. However, GnRH agonist administration at the time of implantation does not improve pregnancy outcome in IUI cycles according to a randomized controlled trial.

Before the IUI

Before artificial insemination is turned to as the solution to impregnate a woman, doctors will require an examination of both the male and female involved in order to remove any and all physical hindrances that are preventing them from naturally achieving a pregnancy. The couple is also given a fertility test to determine the motility, number, and viability of the male's sperm and the success of the female's ovulation (see Tab. 2). From these tests, the doctor may or may not recommend a form of artificial insemination (intrauterine insemination or intracervical insemination).

The sperm used in artificial insemination may be provided by either the woman's partner sperm or by a sperm donation (donor sperm). Though there may be legal, religious and cultural differences in these and other characterizations, the manner in which the sperm is actually used in artifical insemination would be the same, If the procedure is successful, the woman will conceive and carry a baby to term in the normal manner (see Tab. 1). A pregnancy resulting from artificial insemination will be no different from a pregnancy achieved by sexual intercourse. In all cases, the woman would be the biological mother of any child produced by AI, and the male whose sperm is used would be the biological father.

IUI process

Timing is critical, as the window and opportunity for fertilization is little more than twelve hours from the release of the ovum. To increase the chance of success, the woman's menstrual cycle is closely observed, often using ovulation kits, ultrasounds or blood tests, such as basal body temperature tests over, noting the color and texture of the vaginal mucus, and the softness of the nose of her cervix. To improve the success rate of artifical insemination, drugs to create a stimulated cycle may be used, but the use of such drugs also results in an increased chance of a multiple birth.

Sperm can be provided fresh or washed. The washing of sperm increases the chances of fertilization. Pre- and post-concentration of motile sperm is counted. 

When ovarian stimulation is used, patients underwent afirst cycle with orally administered 50 mg/day clomiphene citrate, from days 3 to 7 of the menstrual cycle, along with subcutaneous human menopausal gonadotropin or recombinant FSH at days 3, 5 and 7 of the cycle. The follicular development is monitored by transvaginal ultrasound at days 2 (basal) and 8 of the cycle. Subsequently, daily monitoring is performed until follicular diameter measured 18 to 20 mm and thickness of the endometrium was greater than 7 mm. When one or (at most) three follicles measured the expected mean diameter, hCG or recombinant hCG is administered. IUI is scheduled 36 to 40 hours after hCG or r-hCG administration and confirmation of follicular rupture.

The patient is on bed rest for 20 minutes, and the supplementation of the luteal phase is administered orally with natural progesterone at a dose of 200 mg every 12 h from the day after IUI until confirmation of the embryonic heartbeat using an ultrasound.

Legal aspects of artificial insemination

Some countries restrict artificial insemination in a variety of ways. For example, some countries do not permit AI for single women, and some Muslim countries do not permit the use of donor sperm. As of May 2013, the following European countries permit medically assisted AI for single women: Armenia, Belarus, Belgium, Bulgaria, Cyprus, Denmark, Estonia, Finland, Germany, Greece, Hungary, Iceland, Republic of Ireland, Latvia, Republic of Macedonia, Moldova, Montenegro, Netherlands, Romania, Russia, Spain, Ukraine, United Kingdom.

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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 Cervical mucus defect affect fertility

The cervical mucus is a jelly-like substance produced by minute glands in the cervical canal. It changes in consistency and composition with the menstrual cycle. Just before ovulation and under the effect of the hormone estrogen it becomes very watery and copious to allow the sperm to swim through it. After ovulation and under the effect of progesterone, the mucus becomes thick and sticky, which render it impenetrable to the sperm. Once the sperm are in the mucus, they can stay there for a few days. Thus the mucus acts as a sperm reservoir.

Cervical mucus hostility is the inability of sperm to penetrate the cervical mucus. The significance of cervical mucus hostility is disputable among infertility specialists. Problems with cervical mucus usually cause no symptoms.

The mucus is too sticky and thick (and there is not enough of it to allow sperm to swim through). This may be due to poor estrogen stimulation of the cervical glands (e.g. wrong timing of the test or lack of ovulation) or poor functioning cervical glands due to infection or damage caused by surgery, as may occur after cone biopsy.

Fertile Cervical Mucus
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