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.

Search Results

Nothing found. Please try searching for a different keyword.

Self therapy does not exist.

Conventional medicine does not exist.

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

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%.

See full description of ICSI

Laser-assisted immotile sperm selection

Method, which uses a laser to identify viable sperm cell for subsequent ICSI, recommended in MESA/TESE IVF cycles (surgical sperm retrieval) and any other cases of immotile spermatozoa (severe asthenospermia or necrospermia).
Sperm viability is a prerequisite for a successful ICSI treatment, because the injection of a nonviable spermatozoon into an oocyte generally results in fertilization failure. Normally, the spermatozoa are selected according to motility, which is a clear indication for viability. However, in cases with complete asthenozoospermia, it is impossible to select viable sperm by morphological means.
To identify viable sperm in patients presenting with complete sperm immotility is a challenging but very important step. Using LAISS a single laser shot is applied close to the tip of the sperm tail using a non-contact 1.48 µm diode laser system. In a few seconds, two possible reactions can be observed:
1.    either the tail of the spermatozoa starts curling after the laser shot, or
2.    the spermatozoa show no reaction at all.
Spermatozoa showing a curling reaction are considered to be viable and can be used for ICSI treatment immediately. In contrast to another methods e.g. hypo-osmotic swelling test, the laser selection can be performed directly in IVF medium with no additional micromanipulation.

See full description of Laser-assisted immotile sperm selection

MESA

MESA was first described in 1985. This surgical technique requires testis delivery through a 2-3-cm transverse scrotal incision. The epididymal tunica is incised, and an enlarged tubule is selected. Then, the epididymal tubule is dissected and opened with sharp microsurgical scissors. The fluid that flows out of the tubule is aspirated with the aid of a silicone tube or a needle attached to a tuberculin syringe (Pic.1) The aspirate is flushed into a tube containing warm sperm medium and is transferred to the laboratory for examination. MESA can be repeated at a different site on the same epididymis (from the cauda to caput regions) and/or the contralateral epididymis until an adequate number of motile sperm is retrieved. 

An embryologist examines the sample for the presence of motile sperm. If no motile spermatozoa are found at the first site, the maneuver is repeated. Typically, only a few microliters of epididymal fluid are retrieved because sperm are highly concentrated in the epididymal fluid (approximately 1x106 sperm/ml). A MESA approach should provide more than adequate numbers of sperm for immediate use, as well as for cryopreservation. 

If MESA fails to retrieve motile sperm, TESA or TESE can be performed as part of the same procedure. However, MESA often provides enough sperm for cryopreservation. A single MESA procedure usually enables the retrieval of a large number of high-quality sperm that can be used for ICSI or intentionally cryopreserved for subsequent ICSI attempts. As reported by Dr. Shlegel and colleagues, who used MESA and ICSI in a group of men with obstructive azoospermia, clinical pregnancies were detected by a fetal heartbeat in 75% (57/ 76) of attempts, and healthy deliveries occurred in 64% (49/ 76) of attempts.

ANESTHESIA FOR SPERM RETRIEVAL PROCEDURES Sperm retrievals are relatively simple surgeries that can be safely performed with general anesthesia or spinal blocks. However, because sperm retrievals are typically outpatient procedures, the latest trend is to employ local or locoregional anesthesia with or without intravenous sedation. In another study of 26 patients undergoing MESA, only 38% of the patients tolerated the procedure solely under spermatic cord block through the infiltration of 5-8 mL of 1% lidocaine; the remaining 62% required intravenous sedation. The percentage of patients who underwent a bilateral procedure and required intravenous sedation was as high as 75%.

General anesthesia may offer comfort and the efficient management of anxiety. However, when performed with inhalational agents such as N2O and halogenated agents, this approach is associated with a high incidence of postoperative nausea and vomiting. These two complaints are among the most frequent causes of hospitaliza-tion and the inability to discharge patients scheduled for ambulatory procedures. Additionally, these symptoms are among the most feared by patients undergoing minor surgery, surpassing even postoperative pain.

See full description of MESA

Micro TESE

The concept of micro-TESE is to identify areas of sperm production within the testes with the aid of optical magnification (15-25x) and based on the size and appearance of the seminiferous tubules. Micro-TESE is recommended for the most severe cases of non-obstructive azoospermia (NOA).

MicroTESE yields the highest sperm retrieval rate and causes the least amount of damage to the testis.

Miniinvasive alternative to TESE using microdissection microscope. In microsurgical testicular sperm extraction (microdissection TESE; micro-TESE), the testicular parenchyma is dissected under magnification to search for enlarged seminiferous tubules, which are more likely to contain germ cells and foci of sperm production compared to non-enlarged or collapsed tubules. Such seminiferous tubules are removed rather than proceeding with the large single or multiple biopsies performed in conventional TESE.

For micro-TESE, the scrotal skin is stretched over the anterior surface of the testis, after which a 2 3 cm transverse incision is made. Alternatively, a single midline scrotal incision can be used. The incision extends through the dartos muscle and the tunica vaginalis. The tunica is opened, and identifiable bleeders are cauterized. The testis is delivered extravaginally, and the tunica albuginea is examined. Then, a single, large, mid-portion incision is made in an avascular area of the tunica albuginea under 6-8× magnification, and the testicular parenchyma is widely exposed in its equatorial plane (Pic. 1). The testicular parenchyma is dissected at 16-25× magnification to enable the search and isolation of seminiferous tubules that exhibit larger diameters (which are more likely to contain germ cells and eventually normal sperm production) in comparison to non-enlarged or collapsed counterparts (Pic. 2). If needed, the superficial and deep testicular regions can be examined, and microsurgical-guided testicular biopsies are performed by carefully removing enlarged tubules using microsurgical forceps. If enlarged tubules are not observed, any tubule that differs from the remaining tubules in size is excised. The excised testicular tissue specimens are placed into the inner well of a Petri dish containing sperm media, and are sent to the laboratory for processing and sperm search (Pic. 3). The tunicas albuginea and vaginalis are then closed in a running fashion using non-absorbable and absorbable sutures. The dartos muscle is closed with interrupted absorbable sutures, respectively. Immediately prior to complete closure, 3 cc of 1% xylocaine solution may be injected into the subcuticular layers. The skin is closed using a continuous subcuticular 4-0 vicryl suture. A fluffy-type scrotal dressing and scrotal supporter are placed.

See full description of Micro TESE

PESA

The technical procedure for PESA involves the insertion of a needle attached to a syringe through the scrotal skin into the epididymis (Pic 1). Originally, the use of a larger butterfly needle was described. Currently, most experts use a fine needle (26 gauge) attached to a tuberculin syringe containing sperm washing medium. After creating negative pressure by pulling the syringe plunger, the tip of the needle is gently and slowly moved in and out inside the epididymis until fluid is aspirated. If motile sperm are not obtained, PESA may be repeated at a different site (from the cauda to caput epididymis) until an adequate number of motile sperm is retrieved. These aspirations are usually performed in the corpus epididymis and then in the caput epididymis if needed, as aspirates from the cauda are often rich in poor-quality senescent spermatozoa, debris and macrophages. Because PESA is a blind procedure, multiple attempts may be needed before high-quality sperm are found. If PESA fails to enable the retrieval of motile sperm, testicular sperm retrieval can be attempted during the same operation.
Craft and Shrivastav, in 1994, first described the use of the percutaneous approach to retrieve sperm from the epididymis. Percutaneous retrievals are usually undertaken under local anesthesia only or in association with intravenous sedation. Percutaneous sperm retrieval can be either diagnostic or therapeutic. In the former, it is used to confirm the presence of viable spermatozoa prior to ICSI. In the latter, it is carried out at the same day of oocyte retrieval or at the day before.

See full description of PESA

Preimplantation genetic diagnosis

Pre-implantation genetic diagnosis (PGD) allows couples with a family history of monogenic disorders, x-linked diseases and known chromosomal abnormality to avoid the transfer of embryos with these specific genetic disorders. The first preimplantation diagnosis was performed in 1989 for sex selection due to an X-linked disease. Currently, there are an estimated 10,000 children who were born after preimplantational biopsies.

PGD essentially consists of several steps: 

  1. ovarian superstimulation 
  2. aspiration of ovarian follicles
  3. oocyte retrieval 
  4. intracytoplasmic injection of oocytes with processed sperm
  5. in vitro culture of fertilized oocytes
  6. blastomere biopsy on D3 or trophectoderm biopsy on D5
  7. genetic testing
  8. transfer of a genetically normal embryo

If the blastocyst is not transferred to a receptive uterus until the 5th or 6th day, it loses the ability to produce an embryo. To preserve this possibility, it must be vitrified for later transfer.

Indications of PGD

Indications are similar to conventional prenatal diagnosis with regard to:

a) genetic risks with monogenic or chromosomal causes
b) major predisposition to tumors
c) non-genetic risks
d) selection of the best embryos in IVF laboratories

As PGD involves both an IVF or intracytoplasmic sperm injection (ICSI) procedure and a genetic study, it is mandatory to predict the number of unaffected embryos obtainable for transfer prior to realizing the procedure. The number depends on the embryogenic potential of the fertilized oocytes and the implicated risk according to the genetic disorder. The embryogenic potential depends mainly on the woman's age and the absence of factors that facilitate the production of incompetent gametes. Generally, when a woman is younger than 35 years and the male produces good quality sperm, the embryogenic potential is approximately 50%. The embryogenic potential decreases when a woman's age increases or when sperm is of inferior quality. However, the genetic risk depends on the type of disorder (recessive, dominant, sex-linked) or if the disorder is chromosomal. Table 1 shows the estimated number of embryos needed to have the chance to transfer some unaffected embryos, based on the reasoning of PGD.

PGD technology has several primary applications:

1) Single gene disorders

a) Recessive monogenic disorders

Examples of recessive disorders are congenital disorders such as cystic fibrosis, Tay-Sachs, and thalassemia, which involve two mutated chromosomes from each healthy carrier parent. When the disorder is molecularly characterized, the mutation may be analyzed in cells removed from a cleavage embryo or blastocyst. Minisequencing is the method of choice. However, when the mutation is not known, it might be determined by a linkage study.

In cases where the mutation has not been identified in one of the parents, the use of polymorphic markers linked to the gene of interest could help to provide a better diagnosis and allow to have more transferable embryos; otherwise, embryos carrying the known mutation would be considered as affected when they could be healthy carriers. Today, with the availability of SNParrays, the characterization of individual mutations is no longer needed.

b) Dominant monogenic disorders

Examples of autosomal dominant disorders are myotonic dystrophy, fascio-scapular-humeral dystrophy, retinoblastoma, Von Hippel Lindau, MEN I and II, Huntington's disease, osteogenesis imperfecta, and achondroplasia.

When the patient has a "de novo mutation" it is necessary to sequence the entire gene to identify the mutation. Once the mutation has been characterized, this sequence can be targeted in the cells removed from the embryo. In contrast, when there are several affected members in the family, PGD can also be addressed with polymorphic markers linked to the respective gene.

Usually, Huntington's disease develops late in life or when the offspring are of child-bearing age. Many of them do not want to perform the genetic study because they do not want to know their genetic status in advance, but they want to make sure that their children do not have the mutation. Unlike prenatal diagnosis, PGD for Huntington's disease avoids disclosure of the status of the carrier of the mutation.

It is well known that people with certain genetic disorders live in communities, such as mute communities for congenital deafness or persons with achondroplastic dwarfism, and that these couples desire PGD to increase their likelihood of having similarly affected offspring. This is a situation in which it is difficult to satisfy the parents because the medical team cannot help them.

c) Sex linked genetic disorders

X-linked disorders are transmitted by the healthy carrier mothers to their sons, while the affected males transmit the condition to their grandchildren through their healthy carrier daughters but not through their sons. When the mutation is characterized, it is recommended to perform PGD by minisequencing the mutation. Some reprogeneticists carry out embryo sexing to avoid the birth of males, in such cases, but, this is not recommended.
Examples of recessive X-linked diseases are hemophilia, Fragile X, and Duchenne muscular dystrophy.

In contrast, dominant X-linked diseases are transmitted by affected women to 50% of their daughters and sons, but affected males do not transmit it to their sons. Examples of diseases linked dominant X are Rett syndrome, incontinentia pigmenti, pseudohyperparathyroidism, and vitamin D-resistant rachitism.

As an example of Y-linked disorders, there are some AZF region microdeleted in the long arm of the Y-chromosome. In this case, the only option to avoid transmission to the offspring is female sex selection.

2) Chromosome rearrangements - constitutional chromosomal abnormalities are present in up to 0.9% in newborns, and are associated with 50-60% of first trimester miscarriages. Most of these aneuploidies are a result of a meiotic non-disjunction event, but about 1/500 individuals carry a balanced structural rearrangement as reciprocal and Robertsonian translocations. Although most present with normal phenotypes, they often suffer from repeated spontaneous abortions and/or fertility problems, and have an increased risk of delivering children with congenital anomalies and/or intellectual disability. Several studies have shown that PGD improves the pregnancy outcome for translocation carriers, especially in patients with recurrent pregnancy losses.

3) PGD for Human Leukocyte Antigen HLA typing - people affected by malignant conditions, such as leukaemia, lymphoma or some other disorders as beta-thalassaemia, sickle cell anaemia, Fanconi anaemia, Wiscott-Aldrich syndrome, X-linked adrenoleukodystrophy and hypoimmunoglobulin syndromes, may benefit from allogenic haematopoietic stem cell transplantation (allo-HSCT), using an HLA-matched, related donor, most often a sibling child. PGD techniques are helpful in two situations: (a) one child has a non-inherited disease such as leukaemia and the parents want to have PGD with HLA typing alone to allow the newborn to be a donor to the sick child; or (b) one child has a heritable disorder and the parents need PGD in order to avoid another affected child, and, at the same time, HLA typing brings the hope of saving the already affected sibling. For ethical reasons, in some countries, only the latter procedure is deemed acceptable.

4) PGD for Rh blood group typing

PGD can also be indicated in women who are Rh negative and are highly sensitized with antibodies against Rh factor. If Rh genotyping in the male shows that he is heterozygous, it is feasible to perform a PGD to avoid possible erythroblastosis fetalis and intrauterine blood exchange transfusion. PGD has also been used in women sensitized by other blood factors, such as the Kell/Cellentano group.

5) Sex selection

Some of the clinics that offer PGD provide it for sex selection for non-medical reasons. Nearly half of these clinics perform it only for "family balancing", which is where a couple with two or more children of one sex desire a child of the other, but half do not restrict sex selection to family balancing. In India, this practice has been used to select only male embryos although this practice is illegal. Opinions on whether sex selection for non-medical reasons is ethically acceptable differ widely, as exemplified by the fact that the ESHRE Task Force could not formulate a uniform recommendation.

Genetic methods used in PGD

There are different approaches for examination of the genetic constitution in PGD. Currently, most PGD are using biochemical techniques based on polymerase chain reaction (PCR), wherein the disease-linked loci are amplified from blastomeric DNA using targeted primers designed specifically for the mutation of interest. PCR diagnosis from a single cell is used for the diagnosis of single gene defects or triplet repeat disorders. Microarray-based comparative genomic hybridization (aCGH) is a molecular cytogenetic technique which is performed for detection of chromosomal rearrangements (and also for aneuploidy screening in PGS). The principle of aCGH is complex analysis of chromosomal constitution of the cell using fluorescently labeled nucleotides spotted on a microchip. The result is compared with control DNA which is known to have no genetic alterations. Array CGH has proven to be a specific, sensitive, fast and highthroughput technique, but a main disadvantage is its inability to detect structural chromosomal aberrations without copy number changes, i.e. low-level mosaicism, balanced chromosomal translocations, and inversions. The latest microchip-based technology – karyomapping – targets approximately 300,000 of the most informative markers in the genome for efficient genome-wide coverage, meaning that any single gene disorder can be screened for. Karyomapping is a modern, very fast and progressive method, which allows the detection of mutations combined with aneuploidy screening in one test. This new approach enables two-stage genetic selection of embryos, increasing chances for selecting the most suitable embryo for transfer.

Biopsy techniques used for PGD

There are several biopsy techniques for pre-implantation genetic testing used to evaluate the DNA of embryos before day 6 of conception. 

They are the following:

  • Polar-body biopsy (assessing female gametes), in which oocyte genotype can be deduced by analysis of the first and/or second polar body. Oocytes considered genetically "normal" can then be utilised for IVF. As it is performed before fertilisation, polar-body analysis offers the possibility of preconception diagnosis without reduction in cell number of the embryo. One clear disadvantage is the inability to assess paternal genotype. However, as 95% of aneuploidies arise in maternal meiosis, there is little loss in efficiency for aneuploidy testing.
  • Blastomere biopsy (aspiration), assessing the 3-day, six-to eight-cell cleavage embryo, in which the zona pellucida is traversed to extract one or two cells.
  • Trophectoderm biopsy, assessing the 5-to 6-day, 120-cell blastocyst. Because more cells can be removed at this stage, it potentially facilitates more accurate diagnosis. These additional 2–3 days in culture, beyond that required for an eight-cell embryo, allow some time for natural deselection of non-progressing or aneuploid embryos.
  • Blastocentesis, in blastocysts on D5/D6, as a new type of noninvasive embryo biopsy based on the presence of cells and DNA in the blastocoelic cavity.

See full description of Preimplantation genetic diagnosis

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.

See full description of Preimplantation genetic screening

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.

See full description of Standard IVF

TESE

Testicular sperm extraction (TESE) is the process of removing a small portion of tissue from the testicle under local anesthesia and extracting the few viable sperm cells present in that tissue for intracytoplasmic sperm injection (ICSI).

The testicular sperm extraction process is recommended to men who cannot produce sperm by ejaculation due to azoospermia, such as that caused by primary testicular failure, congenital absence of the vas deferens or non-reconstructed vasectomy.

The introduction of the technique of intracytoplasmic sperm injection to achieve fertilization, especially using surgically retrieved testicular or epididymal sperm from men with obstructive or non-obstructive azoospermia, has revolutionized the field of assisted reproduction. Testicular sperm retrieval techniques associated with intracytoplasmic sperm injection have reduced the need for donor sperm and given many azoospermic men the chance to become biological fathers.

The extraction of the testicular parenchyma for sperm search and isolation was first described in 1995. For conventional TESE, a standard open surgical biopsy technique is used to remove the testicular parenchyma without the aid of optical magnification. This procedure is usually carried out without delivering the testis. Briefly, a 2-cm transverse incision is made through the anterior scrotal skin, dartos and tunica vaginalis. A small self-retaining retractor can be used to ensure proper exposure of the tunica albuginea. A 1-cm incision is made in the albuginea, and gentle pressure is applied to the testis to aid the extrusion of the testicular parenchyma. A fragment of approximately 5x5 mm is excised with sharp scissors and placed in sperm culture media. Single or multiple specimens can be extracted from the same incision. Alternatively, individual albuginea incisions can be made in the upper, middle and lower testicular poles in an organized manner for the sampling of different areas. The testicular specimens are sent to the laboratory for processing and immediate microscopic examination. The tunica albuginea is closed with a running, non-absorbable suture.


See full description of TESE

How can Obstructive azoospermia affect fertility

Obstructive azoospermia is a common urologic condition and accounts for 6.1% to 13.6% of patients presenting for fertility evaluation. Despite being associated with infertility, azoospermia does not necessarily imply sterility. Men with obstructive azoospermia usually produce normal sperm cells in their testes. Although selected cases of OA may be surgically correctable, treatment options for most couples with azoospermia-related infertility will ultimately include assisted reproductive techniques, which is a broad term used to define any procedure that involves handling of both sperm and oocytes outside the body, such as in vitro fertilization (IVF) and its variant, intracytoplasmic sperm injection (ICSI). Assisted reproductive technologies are generally used when the specific cause of obstructive azoospermia cannot be surgically corrected, or the surgical treatment of the condition does not succeed in restoring the patient’s fertility.



Pic. 1: Types of azoospermia
See full description