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Oocyte (Egg) Cryopreservation

Oocyte (egg) freezing is a breakthrough technology that allows women to retrieve, freeze and store their oocyte (egg) indefinitely. Once a pregnancy is desired, the oocyte (egg) can be thawed, fertilized and placed within the uterus in order to initiate a pregnancy. Oocyte (egg) freezing freezing involves several steps as outlined below.
What is oocyte (egg) cryopreservation?

To be stored, an oocyte (egg) is frozen or ‘vitrified’ and stored on the clinic’s premises in a Cryotech freezing device, which can hold a maximum of 2 oocytes (eggs) per device. Standard practice in the laboratory is to freeze two (2) oocytes (eggs) per device to minimise device costs. However, you can elect to freeze an oocyte (egg) individually (1 per device) to facilitate future single embryo transfer and the thawing of one oocyte (egg) at a time. Patients are not guaranteed success at any or all of these steps. If optimal results are not achieved at any step, it may be recommended that the treatment be stopped and the cycle cancelled.

What is Oocyte (egg) Retrieval (Oocyte (egg) Harvest, Follicle Aspiration) and how is it performed?

Oocyte (egg) retrieval is the removal of an oocyte (egg) from the ovary for the purpose of producing a pregnancy. Women take an ovary stimulating medication (some examples of such are – Gonadotropin, Gonal F, Menopur) used to produce several oocytes (eggs). These oocytes (eggs) are then collected from the ovaries using a minor surgical technique known as transvaginal oocyte removal. A transvaginal ultrasound probe is used to visualise the ovaries and the oocyte (egg) containing follicles within the ovaries. A long, hollow needle is threaded alongside of the ultrasound probe. The needle, which can be seen on ultrasound, can then be directed into the follicle and the contents aspirated (withdrawn). The aspirated material includes follicular fluid, oocytes (eggs), and granulosa (egg-supporting) cells. Rarely, the ovaries are not accessible by the transvaginal route and laparoscopy or transabdominal retrieval is necessary. Transvaginal oocyte removal is done under anaesthetic, where an intravenous anaesthesia is used during the procedure (adjunctively) to reduce discomfort. These procedures and risks will be discussed with you by your doctor if applicable.

Risks of oocyte (egg) retrieval?

Infection:
Bacteria normally present in the vagina may be inadvertently transferred into the abdominal cavity by the needle used to retrieve the eggs. These bacteria may cause an infection of the uterus, fallopian tubes, ovaries or other intra-abdominal organs. The estimated incidence of infection after egg retrieval is less than 0.5%. Treatment of infections could require the use of oral or intravenous antibiotics. Severe infections occasionally require surgery to remove infected tissue. Infections can have a negative impact on future fertility. Prophylactic antibiotics are sometimes used before the egg retrieval procedure to reduce the risk of pelvic or abdominal infection in patients at higher risk of this complication. Despite the use of antibiotics, there is no way to eliminate this risk completely.

Bleeding:
The needle passes through the vaginal wall and into the ovary to obtain the eggs. Both of these structures contain blood vessels. In addition, there are other blood vessels nearby. Small amounts of blood loss are common during egg retrievals. The incidence of major bleeding problems has been estimated to be less than 0.1%. Major bleeding will frequently require surgical repair and possibly loss of the ovary. The need for blood transfusion is rare. (Although very rare, review of the world experience with IVF indicates that unrecognized bleeding has led to death).

Trauma:
Despite the use of ultrasound guidance, it is possible to damage other intra-abdominal organs during the egg retrieval. Previous reports in the medical literature have noted damage to the bowel, appendix, bladder, ureters, and ovary. Damage to internal organs may result in the need for additional treatment such as surgery for repair or removal of the damaged organ. However, the risk of such trauma is low.

Failure:
It is possible that the aspiration will fail to obtain any eggs or the eggs may be abnormal or of poor quality and otherwise fail to produce a viable pregnancy.

Anaesthesia:
Usually medications administered by an anaesthesiologist are required for the egg retrieval surgery. You will have a consultation with the anaesthesiologist before the procedure to review the risks and benefits of the anaesthesia. In some cases, the use of anaesthesia on a specific patient may be associated with an increased risk. In such cases the physician may offer local anaesthesia without the assistance of an anaesthesiologist. It is mandatory that you do not drink or eat anything after midnight prior to day of the egg retrieval. After the procedure is completed, you will be discharged home in about an hour. Following any aesthetic, you must be accompanied home by a responsible adult. You are responsible for bringing a responsible adult with you on the day of the egg retrieval. Following the egg retrieval, vaginal spotting and lower abdominal cramping are normal.

During the remainder of the day following the surgery, activities should be limited. If significant bleeding, vomiting, abdominal pain or any other symptoms develop, you should contact your physician. If you should have any difficulty in contacting your physician, you should proceed to the emergency department of the nearest hospital.

Ovulation Induction Medication and/or Hormones?

The oocytes (eggs) are present in the ovaries within fluid-filled cysts called follicles. During a woman’s menstrual cycle, usually one mature follicle develops, which results in the ovulation of a single egg. Several hormones including follicle stimulating hormone (FSH) and luteinizing hormone (LH) influence the growth of the ovarian follicle. These hormones are produced by the pituitary gland, which is located at the base of the brain. FSH is the main hormone that stimulates the growth of the follicle, which produces an oestrogen hormone called estradiol. When the follicle is mature, a large amount of LH is released by the pituitary gland. This surge of LH helps to mature the egg and leads to ovulation 36-40 hours after its initiation.

Medications are administered to increase the number of follicles that develop, which will increase the number of eggs that are obtained at the egg retrieval. The ‘main” medications that are used to cause many follicles to develop. In addition to the gonadotropins you will received another medication to prevent ovulation: a gonadotropin-releasing hormone (GnRH) agonist or antagonist.

Gonadotropins
These are injectable medications commonly prescribed to stimulate the ovaries of women undergoing IVF treatment. Two types of gonadotropins can be prescribed and are discussed below and one or more of them may be prescribed.

  • FSH (Gonal-F, Follistim, Bravelle) – These medications contain only FSH and are administered on a daily basis by injection;
  • LH (Luveris) – This medication contains only LH and is administered by injection. It is used in combination with FSH containing medications;
  • Human Menopausal Gonadotropins (Menopur, Repronex) – These medications contain equal amounts of FSH and LH, and are administered on a daily basis by injection.

GnRH Agonist (Lupron)
This medication is taken by daily injection. The primary role of this medication is to prevent a premature release of the LH from the pituitary gland (the ‘LH surge’), which normally causes the release of eggs (ovulation). Premature ovulation would result in no eggs available to be retrieved and must be prevented by administration of the GnRH agonist or antagnosit medication. GnRH agonist such as Lupron need to be taken for several days before they have their effect to prevent ovulation. Though leuprolide acetate is an FDA (Federal Drug Administration) approved medication, it has not been approved for use in IVF, although it has routinely been used in this way for more than 20 years. Potential side effects usually experienced with long-term use include but are not limited to hot flashes, vaginal dryness, bone loss, nausea, vomiting, reactions at the injection site, fluid retention, muscle aches, headaches, and depression. No long term or serious side effects are known. Since GnRH agonists are often times administered after ovulation in the menstrual prior to beginning treatment, it is possible that they could be taken early in pregnancy. The safest course of action is to use a barrier method of contraception (condoms) during the month that you will be starting the GnRH-a. Sometimes the oral contraceptive pill is used just before the GnRH agonist is started. GnRH agonists have not been associated with any fetal malformations however you should discontinue use of this medication if an inadvertent pregnancy is confirmed.

GnRH Antagonist (Cetrotide, Ganirelix)
GnRH antagonists are medications that reversibly bind to GnRH receptors in the pituitary gland and prevent release of FSH and LH. They perform the same role as GnRH agonists do, to prevent ovulation, but they are typically started on different days and administered for a shorter time since (unlike HnRH agonists) they instantly prevent ovulation when they are started. GnRH antagonists are administered in combination with gonadotropins. The major benefit of a GnRH antagonist is that it suppresses a LH surge thereby preventing ovulation.

Clomiphene Citrate (Clomid, Serophene) and letrozole (Famara)
These medications are rarely used in combination with or in lieu of gonadotropin medications to stimulate egg development. These medications are synthetic hormones that are taken orally for a period of five days and cause the release of FSH and LH, which stimulate the development of follicles.

Human Chorionic Gonadotropin [hCG] (Ovidrel, Profasi, Pregnyl, Novarel)
This medication contains the pregnancy hormone, hCG, which functions similarly to LH. It is administered by injection 36 hours before the egg retrieval to cause the eggs to become mature which will allow them to become fertilized. hCG also loses the microscopic egg from the wall of the follicle so it can be more easily be removed at the egg retrieval.

Oral contraceptive pills
Many treatment protocols include oral contraceptive pills to be taken for 2 to 4 weeks before gonadotropin injections are started in order to suppress hormone production or to schedule a cycle. Side effects include unscheduled.

Medical Risks?

As with all injectable medications, bruising, redness, swelling, or discomfort can occur at the injection site. Rarely, there can be an allergic reaction to these drugs. The use of the above listed medications can cause side effects such as nausea, vomiting, hot flashes, headaches, mood swings, visual symptoms, memory difficulties, joint problems, weight gain and weight loss, all of which are temporary. The intent of giving these medications is to mature multiple follicles, and many women experience some bloating and minor discomfort as the follicles grow and the ovaries become temporarily enlarged. Other possible side effects include the following:

Ovarian Hyper Stimulation
After the egg retrieval is performed, the ovarian follicles, which have been aspirated, can fill up with fluid and form cysts. The formation of cysts will result in ovarian enlargement and can lead to lower abdominal discomfort, bloating and distention. These symptoms generally occur within two weeks after the egg retrieval. The symptoms usually resolve within 1-2 weeks without intervention. If ovarian hyper stimulation occurs, your physician may recommend a period of reduced activity and bed rest. Pregnancy can worsen the symptoms of ovarian hyper stimulation. Severe ovarian hyper stimulation is characterized by the development of large ovarian cysts and fluid in the abdomen and sometimes, the chest. Symptoms of severe ovarian hyper stimulation include abdominal distention and bloating along with weight gain, shortness of breath, nausea, vomiting and decreased urine output. Approximately 2% of women will develop severe ovarian hyper stimulation and may need to be admitted to the hospital for observation and treatment. To help alleviate the symptoms of severe ovarian hyper stimulation an ultrasound-guided paracentesis can be performed which results in the removal of fluid from of the abdominal cavity. Rare, but serious consequences of severe ovarian hyper stimulation include formation of blood clots that can lead to a stroke, kidney damage and possibly death. Every woman who takes these medications can develop ovarian hyper stimulation

Ovarian Torsion (Twisting)
In less than 1% of cases, a fluid filled cyst(s) in the ovary can cause the ovary to twist on itself. This can decrease the blood supply to the ovary and result in significant lower abdominal pain. Surgery may be required to untwist or possibly remove the ovary.

Ovarian Cancer
Some research suggested that the risk of ovarian tumours may increase in women who take any fertility drugs over a long period of time. These studies had significant flaws which limited the strength of the conclusions. Some more recent studies have not confirmed this risk.

Breast and Uterine Cancer
More research is required to examine what the long-term impact of fertility drugs on the development of breast and ovarian cancer. For uterine cancer, the numbers are too small to achieve statistical significance, but it is at least possible that use of fertility drugs may indeed cause some increased risk of uterine cancer.

How long can the embryo(s) be stored?

When considering how long to store for, you may want to think about how far in the future you might want to be able to use your stored embryo(s) and the costs of storing them. Should you decide to freeze and store your embryo(s), you need to be aware that should your embryo(s) remain unclaimed for a period of 10 years, your doctor and/or clinic is obligated to destroy them. Storage fees are ordinarily paid annually in advance. These storage fees will be amended annually, and the clinic will communicate this to you.

Do I/we have any guarantee that the freezing process will be a success?

There is no guarantee, and the clinic accordingly does not warrant, that the embryo(s) will survive the freezing/thawing process or that a successful/viable pregnancy will occur thereafter.

What are the practicalities of cryopreservation?

The practicalities of storage are specified in this document, specifically those issues such as:

  • you and your partner’s (if any) contact details;
  • marital status;
  • the number of embryo(s) per storage device;
  • period of storage and any extension thereof;
  • processes, procedures and equipment; and
  • embryo disposition.

You must consider them carefully and make sure you are aware of what the consequences of your choices are.

Can I speak to someone about this procedure?

Should you wish to be provided with an opportunity to have counselling, in relation to your treatment and storage of your excess embryo(s), then please request the details of a psychologist, who specialises in fertility counselling, from the clinic.

What is an Embryo Disposition Agreement?

An Embryo Disposition Agreement is a written agreement and declaration, entered into between you and your partner, or just you (if single), which specifically regulates and records issues relating to ownership and disposition of your embryo(s). In particular, the agreement and declaration will record what you would like to happen to your embryo(s) if:

  • you or your partner were to pass away;
  • you and your partner were to get divorced/ separated;
  • you or your partner withdraw your consent to be part of the IVF program;
  • you fail to renew your storage agreement or fail to make payment of your storage fees;
  • you (recipient) reach the age of 55 years old (SASREG National Guide Limits); or
  • you or your partner become incapacitated (mentally / physically) and lose the ability to decide for yourself.

It is advised that your wishes, with regards to the future use of the frozen embryo(s), are recorded in an Embryo Disposition Agreement. The reason for this is that in circumstances where you do not have an Embryo Disposition Agreement in place, and you or your partner are no longer able to provide your consent, you and/or your partner will NOT be able to use or have the embryo(s) transferred prior to a court order being obtained.

The clinic will continue to store the embryo(s) until such time as a court order, or suitable settlement agreement, is provided to the clinic. Until the clinic receives the Court Order/ Agreement you both will be equally liable for the storage costs.

While this is perhaps not something you have considered, you and your partner (if any) need to record your wishes on how your embryo(s) are to be used. This must be recorded in a formal written agreement signed by you and your partner (if any). It is therefore recommended that this additional legal step be taken and that you enter into an Embryo Disposition Agreement. You can think of this as an ‘ante-nuptial’ contract for artificial fertilisation.

What if I/we want to donate my/our embryo(s)?

Unused embryo(s) can also be donated to a specific person or an unspecified person (anonymous donation), other than your partner. You can also donate your unused embryo(s) to the clinic for research purposes, therefore helping to increase knowledge about diseases and serious illnesses and potential development of new treatments. Any donation that you would like to make will be recorded in your Embryo Disposition Agreement.

Who will assist me with an Embryo Disposition Agreement?

Should you wish to enter into an Embryo Disposition Agreement, an attorney specialising in Fertility Law, will assist you with the drafting and finalisation thereof. The details of such an attorney can be obtained from the clinic.