Embryo Freezing in IVF Treatment

Embryo Freezing in IVF Treatment

Embryo Freezing in IVF Treatment

Procedure & advantages
What is Embryo Freezing?

What is Embryo Freezing?

The procedure of Embryo freezing is done along with fertility treatment in an IVF laboratory.  It allows people to store gametes, reproductive tissue and embryos for later use. The first successful pregnancy resulting from freezing a healthy embryo took place in the 1980s. Since then, many people have frozen embryos and used them later. If your doctor has given option for frozen embryo transfer you must know the risks and advantages.

Embryo freezing is a laboratory procedure which begins with injection of hormones and other medications to stimulate the production of potentially fertile eggs. The eggs are then extracted from the ovaries, either for fertilizing in a lab or for freezing. A person may wish to freeze their eggs. Or, they may wish to use them at once to become pregnant. Fertilisation of eggs with sperm can be achieved either with in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI).  Often with in vitro fertilisation (IVF) or Intracytoplasmic sperm injection (ICSI) treatment, there may be good quality embryos left over after embryo transfer. Instead of discarding them, there is the option to freeze them to use in the future. A person can also freeze eggs and sperm, which are not fertilized. Embryos can be frozen to preserve fertility so it may be possible to have a baby at a later date.

When freezing is recommended?

Embryo cryopreservation is useful for surplus embryos during in vitro fertilisation. Patients who fail to conceive may become pregnant using frozen embryos in subsequent cycles. Successful patients in IVF treatment may come back later for frozen embryo transfer to achieve a sibling pregnancy.

 

Surplus oocytes or embryos resulting from fertility treatments may be stored for oocyte donation or embryo donation to another woman or couple. At times embryos may be created, frozen and stored specifically for transfer and donation by using donor eggs and sperm.

 When the endometrium is not ready for implantation embryos may be frozen for use at later date. This situation arises in patients with thin endometrium or oocyte donation and surrogacy programme.

 There are certain situations like ovarian hyper stimulation when fresh embryo transfer becomes risky for the woman’s health. In this scenario embryos are frozen for later use.

 Young patients undergoing cancer therapy can freeze their eggs, ovarian or testicular tissue for future use. Rare instances where mother is not fit to undergo a pregnancy may freeze embryos. They can come later for embryo transfer when the health issue is resolved.

How do people freeze embryos?

 

Cryo-preservation or cryo-conservation is a process where cells, tissues or organs are preserved by cooling to very low temperatures. Cryopreservation was applied to humans beginning in 1954 with three pregnancies resulting from the insemination of previously frozen sperm. There are two ways of freezing-

 

Slow freezing: This involves placing the embryos in sealed tubes, then slowly lowering their temperature. It prevents the embryo’s cells from ageing and reduces the risk of damage. However, slow freezing is time-consuming, and it requires expensive machinery.

 

Vitrification: In this process, the tissue is frozen after cryoprotection. The embryos are frozen so quickly that the water molecules do not have time to form ice crystals. This helps protect the embryos and increases their rate of survival during thawing. In the laboratory, large tanks filled with liquid nitrogen are available in which embryos are stored. The embryos remain in sealed containers at temperatures of -321ºF. At this temperature, almost no biological processes, such as ageing, can occur.

  The tanks that contain frozen embryos are monitored 7 days a week. Each tank gets a physical inspection daily, looking for problems or signs of problems. The quantity of nitrogen in the tank is assessed as a means of monitoring for a possible slow leak or an impending tank failure. The nitrogen in the tank is topped up daily, since it continuously evaporates at a slow rate.

When to freeze embryos?

 

Not all embryos are suitable for freezing, so only good quality embryos will be chosen to freeze. Embryos can be frozen at different stages of their development – when they’re just a single cell, at the two to eight cell stage or later in their development (called the blastocyst stage). Eggs and sperm can also be frozen with out fertilising.

 

What is the success rates of thawing frozen embryos?

 

The process of thawing an embryo after cryopreservation has a relatively high success rate, and research suggests that women who use thawed embryos have good chances of delivering healthy babies.

 

How long can embryos stay frozen?

 

Procedures for human embryo freezing were developed in 1984 and only went into widespread use in the late 1980s. This means that the longest time a human embryo has been stored is 25-30 years and, typically, patients that have left embryos in storage for this long are not coming back for them.

In theory, a correctly frozen embryo can remain viable for any length of time. But different laws regulate length of freezing in different countries. Most countries allow freezing up to 10 years.

 

The embryos remain in sealed containers at temperatures of -321ºF. At this temperature, almost no biological processes, such as aging, can occur.

 

Frozen or fresh embryos – which is better?

 

A study published in the International Journal of Reproductive Biomedicine looked at the results of over 1,000 instances of embryo transfer involving either fresh or frozen embryos.

The researchers found no statistical difference between the types of embryos, in terms of pregnancy rates or fetal health.

 

Freezing of human sperm, eggs and embryos @ Femelife

 

Within the laboratory at Femelife we have a tissue bank where we freeze and store oocytes (eggs), sperm and embryos for our patients. The bank has personnel and computerised system for full time monitoring. The procedure is done under supervision of the lab director, and is licensed by the ICMR, Govt of India. All tissue in the bank is stored frozen in liquid nitrogen at a temperature of -196C in vacuum lined tanks that are computer controlled and monitored 7 days a week with a dedicated alarm system. The embryologists are responsible for maintaining the bank and no other employee has access to it.

 

The process of freezing eggs vs. freezing embryos

 

The egg freezing procedure and the embryo freezing procedure both start the same basic way with hormone medication, injected over for 8–12 days, that stimulates the ovaries to produce multiple eggs. Freezing multiple eggs increases the chances of finding healthy eggs later. Study have shown that embryos survive the freeze thaw process better than eggs. The freezing of eggs is a recent procedure and may need further development for wide usage.

  

What are the risks associated with cryopreservation of embryos and human gamete?

 

Risk of contamination

 Since viruses and bacteria can also survive at cryogenic temperatures it needs special attention. The risk of cross-contamination, i.e., transfer of bacteria or other microorganisms from liquid nitrogen to stored samples, is should be taken care. Some investigators have suggested that liquid nitrogen should be sterilised in order to prevent such contamination when so-called open cryodevices, which bring the sample in direct contact with the liquid, are utilised.

 Risk of reduced or lost viability

 Long-term storage does not impact viability/developmental potential of slow-frozen embryos. Cryostorage appears to be safe for slow-frozen oocytes as well.

 

Risk of specimen loss

 In contrast to the risk of infection or time-related decrease in viability, under current practices the risk of loss of cryopreserved gametes and embryos due to human error or equipment failure is relatively high. It is the responsibility of the IVF laboratory to take proper care of the procedure.

 Risks inherent in shipment and handling

 At times, frozen eggs or embryos need transportation for further use according to patient convenience. The shipping procedure carries risk of vessels being exposed to elevated ambient temperature and air pressure, vibration/other physical shock, and horizontal storage.

 A two-step removal of vitrified samples, during which the sample is held in the neck of a dewar in nitrogen vapour for 15 seconds, leads to reduced viability due to thermodynamic instability and devitrification at relatively low temperatures. Cross country transportation of cryopreserved eggs and embryos are guarded by certain laws.

        Embryo freezing is a type of fertility preservation. It may be useful for women with cancer who want to have children after having radiation therapy, chemotherapy, or certain types of surgery, which can cause infertility. Also, called embryo banking and embryo cryopreservation it is widely used in IVF treatment.

 

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Gender Assignment at birth, A Challenge For Parents

Gender Assignment at birth, A Challenge For Parents

Biggest Assignment as a Parent- Raising a child with Genital Ambiguity

The decision to have a baby is the first step in a lifelong commitment of love, time, and financial resources and dealing with a baby with sexual ambiguity is devastating and painful .

Sexual ambiguity is a complex issue. An accurate diagnosis is essential and may take some time. Sex of assignment must be based not only on the underlying diagnosis and karyotype but also on the potential for adult sexual function, fertility, and psychological health. For these reasons, input from several specialties, including endocrinology, genetics, neonatology, psychology, urology, and an ethicist, is important. All members of the team must communicate adequately with each other. Parents must fully understand the medical recommendation for sex assignment and required therapy. They must wholeheartedly agree and support the assigned sex to avoid ambivalence, which can lead to gender confusion and psychological trauma for the child.

Parents may be dealing with two major categories of children presenting with this problem:

  • Virilized 46, XX females –females look like male
  • Under virilized 46, XY males- males look like female

The most common cause of sexual ambiguity in newborns is congenital adrenal hyperplasia secondary to 21-hydroxylase deficiency. Adrenal gland is situated above the kidneys and secretes several hormones.

As a general rule, gonadal tissue containing Y chromosomal material is at higher risk for development of malignancy.

When infant is born with ambiguous genitalia, and the sex of the infant is uncertain, what next ?

Accept the truth, cooperate with medical professionals as further testing is necessary to determine the infant’s sex. Explain all the relevant history during pregnancy that may help in a diagnosis.

 

Reference to more commonly understood birth defects may be useful. Several days may be necessary to complete the testing and a team will participate to make an accurate diagnosis and a considered recommendation.

 

Completion of the birth certificate should not be postponed, and sex assignment should not be delayed. Accept the sex assigned by Medical team.

What can cause genital ambiguity in newborn? Is it preventable?

Drug ingestion, alcohol intake, and ingestion of hormones during pregnancy can lead to such a situation. Hence Maternal history is particularly important. Progestational (androgenic) therapy used for threatened abortion or androgens for endometriosis during pregnancy should be avoided as far as possible. If the mother has signs of excessive androgen or parental family history for occurrence of ambiguity, neonatal deaths, consanguinity, or infertility it can lead to sex disorders.

 

What is the extent of problem?

The most common cause of a virilised female is congenital adrenal hyperplasia (CAH). Virilisation may also be caused by maternal ingestion of androgens or synthetic progesterone during the first trimester of pregnancy. The measurement increased ACTH in blood is useful for making a diagnosis. These babies have female chromosomes with male outlook, however they do have ovaries and uterus like any other female child.

 

An undervirilized male (previously called male pseudo hermaphroditism) refers to a male with female external genitalia. The abnormality may range from various grades of feminisation to a completely female phenotype. Such disorders result from deficient androgen stimulation of genital development and most often are secondary to testosterone biosynthetic defects. These boys have male chromosomes with female outward looks.

How the condition is diagnosed? What are the tests done?

The diagnosis of the origin of sexual ambiguity can rarely be made by examination alone, it is always combined with a series of tests. Tests are directed to determining the presence or absence of palpable gonads (presumably testes), the presence or absence of a uterus, and the karyotype to allows classification of the infant as a virilized female, an under virilized male, having a disorder of gonadal differentiation, or having one of the

unclassified forms. Certain forms of CAH may cause dehydration, hypertension, or areolar or genital hyperpigmentation. Turner’s stigmata may be present, including webbed neck, low hairline, and edema of hands and feet.

Radiographic studies are necessary to find out structural abnormalities like the presence of gonads and other reproductive structures. Pelvic ultrasound examination by qualified and experienced personnel should be performed as soon as

possible to look for a uterus. The presence of gonads, fallopian tubes, and a vaginal vault may also be determined. If necessary, a genitogram may be performed to see the lower reproductive organs like presence of vagina and its extent.

Because 21-hydroxylase deficiency is a common cause of sexual ambiguity, the level of 17-hydroxyprogesterone (17-OHP) should be assessed in all such infants who do not have palpable gonads. Screening of newborns for CAH with measurement of a 17-OHP level is now mandated in all 50 of the United States and in many countries throughout the world. A karyotype is essential and must be obtained expeditiously. Buccal smears are absolutely contraindicated because they are inaccurate. In many laboratories, a karyotype can be completed within 48 to 72 hours.

Defects in testosterone synthesis can be diagnosed by low testosterone levels with defect in its synthesis pathway (from the level of enzymes block either in the adrenal or in testicular pathways).

What is the role of parents in upbringing?

The decision about sex assignment must be carefully made, taking into consideration each “level” of sex determination. Sex assignment also depends on fetal sex hormone exposure, the potential for adult sexual function, and psychological and cultural considerations. It is vital that parents completely understand and support the decision because ambivalence about sex of rearing may result in gender confusion and psychological trauma.

Virilized females are usually assigned a female sex. They have normal ovaries as well as uterus and vaginal structures and, with surgical correction and steroid replacement, can have normal sexual function and achieve fertility. However, severely virilized females should be assigned a male sex.

Undervirilized males are often infertile, and sex assignment has usually been based on

phallic size. Adult social and fulfilling sexual function should be the primary goals of gender assignment. If male sex assignment is contemplated, a trial of depot testosterone (25 mg every 3-4 weeks) for 1 to 3 months indicates whether phallic growth is possible.

In patients with gonadal dysgenesis and Y chromosomal material, gonadectomy is necessary, and fertility is not possible. Internal duct structure is also frequently deranged. Small phallic size usually leads to a female sex assignment.

True hermaphrodites who have a unilateral ovary and uterine structures may have spontaneous puberty and normal fertility and may be raised as females. External genital size and structure may allow male assignment, but more commonly, external genitalia are poorly virilized, and affected infants are assigned a female sex.

 What are the future prospective regarding marriage, child bearing etc.?

Parents must understand that having normal sexual performance does not correlate with reproductive ability. However, physicians always give preference to sexual ability than childbearing probability. Our aim in parenting is to give the child a sexual identity which may contradict the genetic makeup and at places may force us to sacrifice the gonads for future life.

We have much to learn about gender identity and must consider which decisions may be made later than previously thought (e.g., surgery). Some surgical interventions are cosmetic, and some affected patients have expressed the wish to make the decisions in adolescence or adulthood. This field challenges many of our perceptions of sex and gender and our role as physicians. Although the infant with genital ambiguity presents a medical and social emergency, decisions should be made carefully, cautiously, and with all necessary biochemical and anatomic information available. Most important, the multidisciplinary team approach must involve the parents in an open and honest

discussion of the options. In the end, it is the parents who come first in decision making on sex assignment.

A male child be with complete androgen insensitivity should be raised female. Complete androgen insensitivity usually does not have suspicion of ambiguity in the new born period or early childhood. Affected children grow as normal females until puberty. They feminize with normal breast development at puberty because high levels of testosterone are aromatized to oestrogen, but they have no pubic or axillary hair and no menses because they lack uterus and ovaries. Gender identity is usually female. Patients come to medical attention because of lack of menses in adolescent period.

The diagnosis is therefore frequently made when patients are in their middle to late teens. If diagnosed early the testes should be removed to prevent cancer and oestrogen therapy should start early. This therapy helps in developing the vagina and performance as a female is not compromised.

Undervirilized males traditionally, infants with 5-alpha-reductase deficiency were raised as females until puberty, then continued life as males, and, in some cases, achieved fertility. More recently, however, the condition has been recognized early in life, and affected males are now raised from infancy as boys.

Virilized females are usually assigned a female sex. They have normal ovaries as well as

Uterus and ovaries and, with surgical correction and steroid replacement, can have normal sexual function and achieve fertility.

However, severely virilised females should be assigned a male sex. They can perform sexual function as a male but cannot reproduce as they don’t  have male gonads.

Patients with Y-related chromosomal or genetic disorders that cause mal development of one or both testes are said to have gonadal dysgenesis. They present with ambiguous genitalia and may have inadequate virilisation, uterus and vagina may be present in such children. The Y-containing dysgenetic testes are at risk for developing cancer and must be removed better reared as females.

How to deal with infertility in such cases?

Fertility potentiality is decided by karyotyping, presence of gonads and presence of uterus and vagina. Accordingly, they can go for gamete donation programme or surrogacy. The decision has to be taken after discussion with the couple.

 

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