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What is IVF?

IN VITRO FERTILISATION (IVF)

In vitro fertilisation (IVF) is a process of fertilisation where an egg is combined with sperm outside the body, in vitro ("in glass"). 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. After the fertilised egg (zygote) undergoes embryo culture for 2–6 days, it is implanted in the same or another woman's uterus, with the intention of establishing a successful pregnancy.

 

IVF is a type of assisted reproductive technology used for infertility treatment and gestational surrogacy. A fertilised egg may be implanted into a surrogate's uterus, and the resulting child is genetically unrelated to the surrogate. Some countries have banned or otherwise regulate the availability of IVF treatment, giving rise to fertility tourism. Restrictions on the availability of IVF include costs and age, in order for a woman to carry a healthy pregnancy to term. IVF is generally not used until less invasive or expensive options have failed or been determined unlikely to work.

 

In 1978 Louise Brown was the first child successfully born after her mother received IVF treatment. Brown was born as a result of natural-cycle IVF, where no stimulation was made. The procedure took place at Dr Kershaw's Cottage Hospital (now Dr Kershaw's Hospice) in Royton, Oldham, England. Robert G. Edwards was awarded the Nobel Prize in Physiology or Medicine in 2010. The physiologist co-developed the treatment together with Patrick Steptoe and embryologist Jean Purdy but the latter two were not eligible for consideration as they had died and the Nobel Prize is not awarded posthumously.

 

With egg donation and IVF, women who are past their reproductive years, have infertile male partners, have idiopathic female-fertility issues, or have reached menopause can still become pregnant. Adriana Iliescu held the record for a while as the oldest woman to give birth using IVF and a donor egg, when she gave birth in 2004 at the age of 66. In September 2019, a 74-year-old woman became the oldest-ever to give birth after she delivered twins at a hospital in Guntur, Andhra Pradesh. After the IVF treatment, some couples get pregnant without any fertility treatments. In 2018 it was estimated that eight million children had been born worldwide using IVF and other assisted reproduction techniques.

 

Indications
IVF may be used to overcome female infertility when it is due to problems with the fallopian tubes, making in vivo fertilisation difficult. It can also assist in male infertility, in those cases where there is a defect in sperm quality; in such situations intracytoplasmic sperm injection (ICSI) may be used, where a sperm cell is injected directly into the egg cell. This is used when sperm has difficulty penetrating the egg. In these cases the partner's or a donor's sperm may be used. ICSI is also used when sperm numbers are very low. When indicated, the use of ICSI has been found to increase the success rates of IVF.

 

According to UK's NICE guidelines, IVF treatment is appropriate in cases of unexplained infertility for women who have not conceived after 2 years of regular unprotected sexual intercourse.

 

In women with anovulation, it may be an alternative after 7 - 12 attempted cycles of ovulation induction, since the latter is expensive and more easy to control.

 

Success rates
IVF success rates are the percentage of all IVF procedures that result in a favourable outcome. Depending on the type of calculation used, this outcome may represent the number of confirmed pregnancies, called the pregnancy rate, or the number of live births, called the live birth rate. The success rate depends on variable factors such as maternal age, cause of infertility, embryo status, reproductive history, and lifestyle factors.

 

Maternal age: Younger candidates of IVF are more likely to get pregnant. Women older than 41 are more likely to get pregnant with a donor egg.

 

Reproductive history: Women who have been previously pregnant are in many cases more successful with IVF treatments than those who have never been pregnant.

 

Due to advances in reproductive technology, IVF success rates are substantially higher today than they were just a few years ago.

 

Live birth rate
The live birth rate is the percentage of all IVF cycles that lead to a live birth. This rate does not include miscarriage or stillbirth; multiple-order births, such as twins and triplets, are counted as one pregnancy.

 

Pregnancy rate
Pregnancy rate may be defined in various ways. In the United States, the pregnancy rate used by the Society for Assisted Reproductive Technology and the Centers for Disease Control are based on fetal heart motion observed in ultrasound examinations.

 

Predictors of success
The main potential factors that influence pregnancy (and live birth) rates in IVF have been suggested to be maternal age, duration of infertility or subfertility, bFSH and number of oocytes, all reflecting ovarian function. Optimal woman's age is 23–39 years at time of treatment.

 

Antral follicle count, with higher count giving higher success rates. Anti-Müllerian hormone levels, with higher levels indicating higher chances of pregnancy, as well as of live birth after IVF, even after adjusting for age. Factors of semen quality for the sperm provider.

 

Characteristics of cells from the cumulus oophorus and the membrana granulosa, which are easily aspirated during oocyte retrieval. These cells are closely associated with the oocyte and share the same microenvironment, and the rate of expression of certain genes in such cells are associated with higher or lower pregnancy rate.

 

Methods
IVF could be performed by collecting the contents from a woman's fallopian tubes or uterus after natural ovulation, mixing it with sperm, and reinserting the fertilised ova into the uterus. However, without additional techniques, the chances of pregnancy would be extremely small. The additional techniques that are routinely used in IVF include ovarian hyperstimulation to generate multiple eggs, ultrasound-guided transvaginal oocyte retrieval directly from the ovaries, co-incubation of eggs and sperm, as well as culture and selection of resultant embryos before embryo transfer into a uterus.


  • Ovarian hyperstimulation
  • Final maturation induction
  • Egg and sperm preparation
  • Embryo culture
  • Embryo transfer
  • Ovulation induction
  • Natural IVF
  • Egg retrieval
  • Co-incubation
  • Embryo selection
  • Luteal support

Because the IVF process bypasses the fallopian tubes (it was originally developed for women with blocked or missing fallopian tubes), it is the procedure of choice for those with fallopian tube issues, as well as for such conditions as endometriosis, male factor infertility and unexplained infertility. A physician can review a patient's history and help to guide them to the treatment and diagnostic procedures that are most appropriate for them.

IVF must only be done on women where it is actually indicated. It is indicated in the following situations where natural or IUI conception is difficult:

  • Women who have been trying for many years and have undergone at least 4 IUI would be recommended IVF as they are unexplained infertility and where cause is not known IVF does what is not happening in the body.
  • Bilateral tubal block: When both tubes are blocked the egg cannot reach the womb. In this case IVF is the only option as in IVF the egg is taken out fertilized with sperm and put back.
  • Very low sperm count and motility of sperm – The sperm does not have the capacity to swim up and fertilize the egg. In this case IVF helps as this is done outside the body.
  • Poor egg reserve – In older women or those with premature ovarian failure the quantity and quality of eggs go down. In that case a donor egg is required which is fertilized with husbands sperm and then deposited in the uterus.
  • Surgically removed uterus or where the uterus is damaged as with severe tuberculosis – Surrogacy can be done where the embryo is deposited in a woman who carries the baby to term.
  • Absent sperms in semen – testicular sperm aspiration or micro test is used to extract sperms from testis These sperms fertilize the egg through ICSI and the resulting embryo is deposited in the uterus.
  • PGD: In case one partner is afflicted with a genetic disease IVF is done and the resulting embryo is biopsied (PGD) to check for that genetic disease. Only that embryo is transferred in uterus which are genetically normal.
  • Severe endometriosis.
  • PCOS not responding to simple treatment like IUI.
  • While some research suggests a slightly higher incidence of birth defects in IVF-conceived children compared with the general population (4 - 5% vs. 3%), it is possible that this increase is due to factors other than IVF treatment itself.
  • It is important to recognize that the rate of birth defects in the general population is about 3% of all births for major malformations and 6% if minor defects are included. Recent studies have suggested that the rate of major birth defects in IVF-conceived children may be on the order of 4 to 5%. This slightly increased rate of defects has also been reported for children born after IUI and for naturally-conceived siblings of IVF children, thus it is possible that the risk factor is inherent in this particular patient population rather than in the technique used to achieve conception.
  • Research indicates that IVF-conceived children are on par with the general population in academic achievement as well as with regards to behavioral and psychological health. More studies are under way to further investigate this important issue.

The prospect of daily injections can be overwhelming. While injections are a necessary part of IVF treatment, we have designed our medication schedules and injection type to minimize discomfort and stress; and our nurses carefully instruct and support every patient throughout this process. Medications that once had to be injected into the muscle have been replaced by medications given as a small injection under the skin (subcutaneous). Such injections are most commonly taken over a 10-12 day period, followed by one intramuscular injection of hCG, a hormone that triggers ovulation at the conclusion of the stimulation cycle. The hCG injection, previously only available in an intramuscular form, is now available in a subcutaneous form (Ovidrel) for patients that wish to avoid intramuscular injection. Although the recombinant subcutaneous form of hCG in Ovidrel has not been around as long as intramuscular hCG, all indications are that it is just as effective.

 

After egg retrieval, patients are given a progesterone hormone supplement in order to prepare the lining of the uterus for the embryo transfer. For most patients, progesterone may be taken in a vaginal tablet or vaginal suppository form rather than an injection. In this way, injections may be avoided entirely during the second half of the IVF cycle. Progesterone vaginal tablets and suppositories have been proven to be as effective as progesterone injections.

Because anesthesia is used for egg retrieval, patients feel nothing during the procedure. Egg retrieval is a minor surgery, in which a vaginal ultrasound probe fitted with a long, thin needle is passed through the wall of the vagina and into each ovary. The needle punctures each egg follicle and gently removes the egg through a gentle suction. Anesthesia wears off quickly once egg retrieval is concluded. Patients may feel some minor cramping in the ovaries that can be treated with appropriate medications.

Most of our out of town patients return home the day after the embryo transfer -- there is no medical reason to stay in San Francisco after IVF treatment. All types of travel are safe. Sitting for an extended period of time will not affect chances of pregnancy. We recommend that patients traveling by air drink plenty of fluids, as circulated air can be quite dry, and dehydration should be avoided.

A woman's ovaries house hundreds of potential eggs. Each month, during the natural ovulation cycle, the ovary selects just one egg from a pool of 100-1,000. Those eggs which are not selected undergo a natural cell death process called atresia. When a woman uses fertility medication, the body's natural selection process is overridden, and a number of these otherwise unused eggs are allowed to grow. As many as 20 eggs may be stimulated in a given cycle. Thus when using fertility medication in the IVF process, not only is the woman not using up all of her eggs, but she is 'rescuing' eggs that otherwise would have undergone atresia.

  • The quality and survival of the frozen-thawed embryos. In general, we only freeze good quality embryos so the current rate of survival is greater than 90%.
  • The age of the woman who produced the eggs. In patients under the age of 37, the chances of pregnancy with frozen-thawed embryos are similar to a pregnancy with fresh embryos.
  • In patients 37 years or older, pregnancy chances with frozen-thawed embryos decline in conjunction with declining fertility in general, but still can be quite good. As always it is best to discuss a woman's individual situation with their physician.
  • The status of the uterus in the woman receiving the embryos. A healthy endometrial lining free of any interfering fibroids or polyps provides a sound environment for embryo implantation.

Previously frozen embryos may be transferred during a woman's natural cycle or in a controlled (artificial) cycle, depending on a number of factors:

  • Controlled cycle transfer
    In a controlled cycle, hormone medications are given to prepare the uterus for transfer. This method is recommended for patients who have irregular cycles. Because the controlled cycle can be precisely timed, it is also advised for those who are on a set travel schedule. The medications commonly used for a controlled cycle are estrogen (either in an injectable or oral form) and progesterone (in either an injectable or vaginal form).
  • Patients who have a regular menstrual cycle may have the option of using their natural cycle for transfer of frozen-thawed embryos. In this case, there is no need for hormone treatment, as the body's natural cycle will prepare the uterus for pregnancy. In cases where natural cycle transfer is possible, this option allows for less medication and monitoring and thus is often relatively affordable for patients. We typically will monitor the natural cycle using home urinary ovulation predictor kits as well as ultrasounds. When the kit changes and/or a nice pre-ovulatory follicle is seen on ultrasound, we administer a single injection of Ovidrel (recombinant subcutaneous hCG) and the patient starts progesterone vaginal suppositories a couple of days later. The embryo transfer will occur 5-7 days after ovulation/hCG injection, depending on whether the embryos are frozen at a Day 3 or Day 5 stage.
  • For the transfer procedure itself, the embryo is thawed at room temperature, and then warmed to body temperature (37° C). As with a fresh embryo transfer, embryos are placed inside a special catheter (a very thin tube), which is guided through the cervix and into the uterus. Embryos are gently injected into the uterus and the catheter is removed. This procedure requires no anesthesia, and is done in a position similar to a pelvic examination for a Pap smear. After transfer, the woman rests for 15 minutes and then is able to go home, where a day of rest or very gentle daily activity is recommended.

The ability to use a donor egg has enabled thousands of women to become pregnant when they otherwise might not have had this opportunity. While a woman's eggs may not be viable, very often the uterus is completely healthy and capable of supporting a pregnancy. In these cases, egg donation with IVF has high success rates. This procedure follows the same protocol as IVF, except the intended parents select a donor and use the donor's egg to create the embryo. Patients may seek egg donation services at Pacific Fertility Center's Egg Donor Agency or at an outside agency.

  • There are two types of gestational carriers
    A traditional gestational carrier becomes artificially inseminated with the sperm of the intended father and uses her own eggs to fertilize the embryo. Many fertility centers, including Pacific Fertility Center do not offer traditional surrogacy. The legal issues and complicated past history of parental rights with traditional surrogacy have led us to discourage this option.
  • A gestational carrier with IVF does not contribute any of her own genetic material. In this case, the egg as well as sperm are extracted from the prospective parents, fertilized in the laboratory with IVF and then implanted into the uterus of the surrogate.
  • A gestational carrier may be appropriate for those in the following situations
    No uterus
  • Abnormal uterine cavity
  • Several recurrent miscarriages
  • Recurrent IVF cycles have not produced a pregnancy
  • Medical conditions would make pregnancy dangerous for the mother or her baby

Various medical conditions may make it impossible for a woman to carry a pregnancy. Reproductive medicine provides the option of enabling another woman, known as a gestational carrier (formerly called a surrogate) to carry the child of a woman who cannot sustain a pregnancy.

  • There are two types of gestational carriers
    A traditional gestational carrier becomes artificially inseminated with the sperm of the intended father and uses her own eggs to fertilize the embryo. Many fertility centers, including Pacific Fertility Center do not offer traditional surrogacy. The legal issues and complicated past history of parental rights with traditional surrogacy have led us to discourage this option.
  • A gestational carrier with IVF does not contribute any of her own genetic material. In this case, the egg as well as sperm are extracted from the prospective parents, fertilized in the laboratory with IVF and then implanted into the uterus of the surrogate.
  • A gestational carrier may be appropriate for those in the following situations
    No uterus
  • Abnormal uterine cavity
  • Several recurrent miscarriages
  • Recurrent IVF cycles have not produced a pregnancy
  • Medical conditions would make pregnancy dangerous for the mother or her baby