Oocyte cryopreservation

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ICSI sperm injection into oocyte Icsi.JPG
ICSI sperm injection into oocyte

Oocyte cryopreservation is a procedure to preserve a woman's eggs (oocytes). This technique is often used to delay pregnancy. When pregnancy is desired, the eggs can be thawed, fertilized, and transferred to the uterus as embryos. Several studies have shown that most infertility problems are due to germ cell deterioration related to aging. [1] The procedure's success rate varies depending on the woman's age (with higher odds of success in younger women), health, and genetic factors. The first human birth of oocyte cryopreservation was reported in 1986. [2]

Contents

Indications

Women diagnosed with cancer who have not yet begun chemotherapy or radiotherapy can benefit from Oocyte cryopreservation. [3] Chemotherapy and radiotherapy are toxic to oocytes, reducing the number of viable eggs. Egg-freezing may be used in this case to preserve eggs as opposed to Oocyte cryopreservation.[ clarification needed ][ citation needed ]

Those undergoing treatment with assisted reproductive technologies who do not consider embryo freezing an option often look towards Oocyte cryopreservation as an alternative option.

Women who would like to preserve their future ability to have children often use Oocyte cryopreservation to delay and freeze their eggs, allowing for them to have children later in life.

Women with a family history of early menopause may have an interest in fertility preservation to preserve viable eggs that could deteriorate at an earlier onset.

Those with ovarian diseases such as Polycystic Ovary Syndrome.[ citation needed ]

Oocyte cryopreservation is one of many options for individuals undergoing IVF. In some cases, persons may prefer oocyte cryopreservation over other options, where freezing embryos is the primary procedure.

Method

The egg retrieval process for oocyte cryopreservation is the same as that for in vitro fertilization (IVF). This includes one to several weeks of hormone injections that stimulate ovaries to ripen multiple eggs. When the eggs are mature, final maturation induction is performed. [4] The eggs are subsequently removed from the body by transvaginal oocyte retrieval. The procedure is usually conducted under sedation. The eggs are immediately frozen. [5]

The egg is the largest cell in the human body and contains a large amount of water. When the egg is frozen, the ice crystals that form can destroy the integrity of the cell. To prevent this, the egg must be dehydrated before freezing. This is done using cryoprotectants which replace most of the water within the cell and inhibit the formation of ice crystals.

Eggs (oocytes) are frozen using either a controlled rate, a slow-cooling method, or a newer flash-freezing process known as vitrification. Vitrification is much faster but requires higher concentrations of cryoprotectants to be added. The result of vitrification is a solid glass-like cell, free of ice crystals. Vitrification has been developed and successfully applied in IVF treatment with the first live birth following the vitrification of oocytes achieved in 1999. [6] Vitrification eliminates ice formation inside and outside of oocytes on cooling, during cryostorage, and as the oocytes warm. Vitrification is associated with higher survival rates and enhanced development compared to slow-cooling when applied to oocytes in metaphase II. [7] Vitrification has also become the method of choice for pronuclear oocytes, although prospective randomized controlled trials are still lacking. [7]

During the freezing process, the zona pellucida, or shell of the egg, can be modified preventing fertilization. Thus, when eggs are thawed and pregnancy is desired, a fertilization procedure known as ICSI (Intracytoplasmic Sperm Injection) is performed by an embryologist whereby sperm is injected directly into the egg with a needle rather than allowing sperm to penetrate naturally by placing it around the egg in a dish.

Immature oocytes have been grown until maturation in vitro , but it is not yet clinically available. [8]

Success rates

Early work investigating the percentage of transferred cycles showed lower frozen cycles compared with fresh cycles (approx. 30% and 50%), [9] however more recent studies show "fertilization and pregnancy rates are similar to IVF/ICSI (in vitro fertilization/intracytoplasmic sperm injection) with fresh oocytes when [both] vitrified and warmed oocytes are used as part of IVF/ICSI". [10] These studies were completed mostly in young patients.

In a 2013 meta-analysis of more than 2,200 cycles using frozen eggs, scientists found the probability of having a live birth after three cycles was 31.5% for women who froze their eggs at age 25, 25.9% at age 30, 19.3% at age 35, and 14.8% at age 40. [11]

Studies have shown that the rate of birth defects and chromosomal defects when using cryopreserved oocytes is consistent with that of natural conception. [12] [13]

Recent modifications in the protocol regarding cryoprotectant composition, temperature, and storage methods have had a large impact on the technology, and while it is still considered an experimental procedure, it is quickly becoming an option for women. Slow freezing traditionally has been the most commonly used method to cryopreserve oocytes and is the method that has resulted in the most babies born from frozen oocytes worldwide. Ultra-rapid freezing or vitrification represents a potential alternative freezing method.

In the fall of 2009, The American Society for Reproductive Medicine (ASRM) issued an opinion on oocyte cryopreservation concluding that the science holds "great promise for applications in oocyte donation and fertility preservation" because recent laboratory modifications have resulted in improved oocyte survival, fertilization, and pregnancy rates from frozen-thawed oocytes in IVF. [14] The ASRM noted that from the limited research performed to date, there does not appear to be an increase in chromosomal abnormalities, birth defects, or developmental deficits in the children born from cryopreserved oocytes. The ASRM recommended that pending further research, oocyte cryopreservation should be introduced into clinical practice on an investigational basis and under the guidance of an Institutional Review Board (IRB). As with any new technology, safety and efficacy must be evaluated and demonstrated through continued research.

In October 2012, the ASRM lifted the experimental label from the technology for women with a medical need, citing success rates in live births, among other findings. However, they also warned against using it only to delay child-bearing.

In 2014, a Cochrane systematic review was published. It compared vitrification (the newest technology) versus slow freezing (the oldest one). Key results of that review showed that the clinical pregnancy rate was almost 4 times higher in the oocyte vitrification group than in the slow-freezing group, with moderate quality of evidence. [15]

Immature oocytes have been grown until maturation in vitro at a 10% survival rate, but no experiment has been performed to fertilize such oocytes. [8]

Cost

The cost of the egg-freezing procedure (without embryo transfer) in the United States, the United Kingdom, and other European countries varies in between $5,000 and $12,000. The cost of egg storage can vary from $100 to more than $1,000. Provisional health programs do not cover social egg freezing. Furthermore, no provinces provide funding for IVF after social egg freezing. [16]

Medical tourism may have lower costs than performing egg freezing in high-cost countries like the US. Some well-established medical tourism and IVF countries such as the Czech Republic, Ukraine, and Cyprus offer egg freezing at competitive prices. It is a lower-cost alternative to typical US options for egg freezing. Spain and the Czech Republic are popular destinations for this treatment.

Iranian insurance started to pay insurance incentives for women freezing their eggs in 2024. [17]

History

Cryopreservation itself has always played a central role in assisted reproductive technology. With the first cryopreservation of sperm in 1953 and of embryos twenty five years later, these techniques have become routine. Dr. Christopher Chen of Singapore reported the world's first pregnancy in 1986 using previously frozen oocytes. [2] This report stood alone for several years followed by studies reporting success rates using frozen eggs to be much lower than those of traditional in vitro fertilization (IVF) techniques using fresh oocytes. Providing the lead to a new direction in cryobiology, Dr. Lilia Kuleshova was the first scientist to achieve vitrification of human oocytes that resulted in a live birth in 1999. [6] Articles published in the journal Fertility and Sterility reported that pregnancy rates using frozen oocytes that were comparable to those of cryopreserved embryos and even fresh embryos. [18] [19] [20]

Elective oocyte cryopreservation

Elective oocyte cryopreservation, also known as social egg freezing, is non-essential egg freezing to preserve fertility for delayed child-bearing when natural conception becomes more problematic. The frequency of this procedure has steadily increased since October 2012 when the American Society for Reproductive Medicine (ASRM) lifted the 'experimental' label from the process. [21] There was a spike in interest in 2014 when global corporations Apple and Meta Platforms announced they were going to pay for the procedure of egg freezing as a benefit for their female employees. [22] This announcement was controversial as some women found it empowering and practical, while others viewed the message these companies were sending to women trying to have a successful long-term career and a family as harmful and alienating. A string of "egg-freezing parties" hosted by third-party companies have also helped popularize the concept among young women. [23] Social science research suggests that women use elective egg freezing to disentangle their search for a romantic partner from their plans to have children. [24]

In 2016, then US Secretary of Defense Ash Carter announced that the Department of Defense would cover the cost of freezing sperm or eggs through a pilot program for active duty service members, to preserve their ability to start a family even if they sustain certain combat injuries. [25]

There are still warnings for women using this technology to fall pregnant at an older age as the risk of pregnancy complications increases with a mother's age. However, studies have shown that the risk of congenital abnormalities in babies born from frozen oocytes is not increased further when compared to naturally conceived babies. [26]

Risks

The risks associated with egg freezing relate to the administration of medications to stimulate the ovaries and the procedure of egg collection.

The main risk associated with the administration of medications to stimulate the ovaries is ovarian hyperstimulation syndrome (OHSS). This is a transient syndrome in which there is increased permeability of the blood vessels, resulting in fluid loss from the vessels into the surrounding tissues. In most cases, the syndrome is mild, with symptoms such as abdominal bloating, mild discomfort, and nausea. In moderate OHSS there is increased abdominal bloating resulting in pain and vomiting. Reduced urine output may occur. Severe OHSS is serious with even further bloating so that the abdomen appears very distended, and thirst and dehydration occur with minimal urine output. There may be shortness of breath and there is an increased risk of DVT and/or pulmonary embolism. Kidney and liver function can be compromised. Hospitalization under specialist care is indicated. There is no treatment for OHSS, supportive care until the symptoms naturally resolve is required. If an hCG trigger has been used with no embryo transfer, OHSS usually resolves in 7–10 days. If an embryo transfer has occurred and pregnancy results, the symptoms may persist for several weeks. Doctors reduce the likelihood of OHSS occurring by decreasing the doses of gonadotropins (FSH) administered, using a GnRH agonist trigger (instead of an hCG trigger), and freezing all embryos for transfer rather than conducting a fresh embryo transfer.

Risks associated with the egg collection procedure relate to bleeding and infection. The collection procedure involves passing a needle through the wall of the vagina into vascular-stimulated ovaries. A small amount of bleeding is inevitable. In rare cases, there is excessive bleeding into the abdomen requiring surgery. Women undergoing the procedure must advise their specialist of all medications, including herbal supplements, they are using so the specialist can assess whether any of these medications will affect the ability of the blood to clot. Concerning infection, provided the woman does not have additional risk factors for infection (suppressed immune system, use of immuno-suppressive medications, or large ovarian endometriomas) the risk of infection is very low.

One additional risk of the ovaries being temporarily increased in size is ovarian torsion. Ovarian torsion occurs when an enlarged ovary twists around on itself, cutting off its blood supply. The condition is excruciatingly painful and requires urgent surgery to prevent the ischemic loss of the ovary.

See also

Related Research Articles

<span class="mw-page-title-main">In vitro fertilisation</span> Assisted reproductive technology procedure

In vitro fertilisation (IVF) is a process of fertilisation in which an egg is combined with sperm in vitro. The process involves monitoring and stimulating a woman's ovulatory process, then removing an ovum or ova from her ovaries and enabling a man's sperm to fertilise them in a culture medium in a laboratory. After a fertilised egg (zygote) undergoes embryo culture for 2–6 days, it is transferred by catheter into the uterus, with the intention of establishing a successful pregnancy.

<span class="mw-page-title-main">Assisted reproductive technology</span> Methods to achieve pregnancy by artificial or partially artificial means

Assisted reproductive technology (ART) includes medical procedures used primarily to address infertility. This subject involves procedures such as in vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI), cryopreservation of gametes or embryos, and/or the use of fertility medication. When used to address infertility, ART may also be referred to as fertility treatment. ART mainly belongs to the field of reproductive endocrinology and infertility. Some forms of ART may be used with regard to fertile couples for genetic purpose. ART may also be used in surrogacy arrangements, although not all surrogacy arrangements involve ART. The existence of sterility will not always require ART to be the first option to consider, as there are occasions when its cause is a mild disorder that can be solved with more conventional treatments or with behaviors based on promoting health and reproductive habits.

<span class="mw-page-title-main">Embryo transfer</span> Method of assisted reproduction

Embryo transfer refers to a step in the process of assisted reproduction in which embryos are placed into the uterus of a female with the intent to establish a pregnancy. This technique - which is often used in connection with in vitro fertilization (IVF) - may be used in humans or in other animals, in which situations and goals may vary.

Ovarian hyperstimulation syndrome (OHSS) is a medical condition that can occur in some women who take fertility medication to stimulate egg growth, and in other women in sporadic cases. Most cases are mild, but rarely the condition is severe and can lead to serious illness or even death.

Egg donation is the process by which a woman donates eggs to enable another woman to conceive as part of an assisted reproduction treatment or for biomedical research. For assisted reproduction purposes, egg donation typically involves in vitro fertilization 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 assisted reproductive technology.

Autologous Endometrial Coculture is a technique of assisted reproductive technology. It involves placing a patient’s fertilized eggs on top of a layer of cells from her own uterine lining, creating a more natural environment for embryo development and maximizing the chance for an in vitro fertilization (IVF) pregnancy.

Controlled ovarian hyperstimulation is a technique used in assisted reproduction involving the use of fertility medications to induce ovulation by multiple ovarian follicles. These multiple follicles can be taken out by oocyte retrieval for use in in vitro fertilisation (IVF), or be given time to ovulate, resulting in superovulation which is the ovulation of a larger-than-normal number of eggs, generally in the sense of at least two. When ovulated follicles are fertilised in vivo, whether by natural or artificial insemination, there is a very high risk of a multiple pregnancy.

<span class="mw-page-title-main">In vitro maturation</span> Artificial maturation of harvested immature egg cells

In vitro maturation (IVM) is the technique of letting the contents of ovarian follicles and the oocytes inside mature in vitro. It can be offered to women with infertility problems, combined with In Vitro Fertilization (IVF), offering women pregnancy without ovarian stimulation.

Poor ovarian reserve is a condition of low fertility characterized by 1): low numbers of remaining oocytes in the ovaries or 2) possibly impaired preantral oocyte development or recruitment. Recent research suggests that premature ovarian aging and premature ovarian failure may represent a continuum of premature ovarian senescence. It is usually accompanied by high FSH levels.

Transvaginal oocyte retrieval (TVOR), also referred to as oocyte retrieval (OCR), is a technique used in in vitro fertilization (IVF) in order to remove oocytes from an ovary, enabling fertilization outside the body. Transvaginal oocyte retrieval is more properly referred to as transvaginal ovum retrieval when the oocytes have matured into ova, as is normally the case in IVF. It can be also performed for egg donation, oocyte cryopreservation and other assisted reproduction technology such as ICSI.

Fertility preservation is the effort to help cancer patients retain their fertility, or ability to procreate. Research into how cancer, ageing and other health conditions effect reproductive health and preservation options are growing. Specifically sparked in part by the increase in the survival rate of cancer patients.

<span class="mw-page-title-main">Cryopreservation</span> Process to preserve biological matter

Cryopreservation or cryoconservation is a process where biological material - cells, tissues, or organs - are frozen to preserve the material for an extended period of time. At low temperatures any cell metabolism which might cause damage to the biological material in question is effectively stopped. Cryopreservation is an effective way to transport biological samples over long distances, store samples for prolonged periods of time, and create a bank of samples for users. Molecules, referred to as cryoprotective agents (CPAs), are added to reduce the osmotic shock and physical stresses cells undergo in the freezing process. Some cryoprotective agents used in research are inspired by plants and animals in nature that have unique cold tolerance to survive harsh winters, including: trees, wood frogs, and tardigrades. The first human corpse to be frozen with the hope of future resurrection was James Bedford's, a few hours after his cancer-caused death in 1967.[15] Bedford's is the only cryonics corpse frozen before 1974 still frozen today.

The Genetics & IVF Institute (GIVF) is an international provider of infertility and genetics services and products, and also engages in biomedical research in these fields. The Institute was founded in 1984 by Dr. Joseph D. Schulman and associates. GIVF headquarters are in Fairfax, VA, US, and its facilities include locations in Pennsylvania, Minnesota, California, and Texas in the United States, as well as in China, Mexico, and several other countries.

Ovarian tissue cryopreservation is cryopreservation of tissue of the ovary of a female.

Oocyte selection is a procedure that is performed prior to in vitro fertilization, in order to use oocytes with maximal chances of resulting in pregnancy. In contrast, embryo selection takes place after fertilization.

Cryopreservation of embryos is the process of preserving an embryo at sub-zero temperatures, generally at an embryogenesis stage corresponding to pre-implantation, that is, from fertilisation to the blastocyst stage.

Natural Cycle In Vitro Fertilization (IVF) is an assisted reproductive technique designed to closely mimic a woman's natural menstrual cycle. In traditional IVF, a woman's ovaries are stimulated with fertility medications to produce multiple eggs, which are then retrieved and fertilized outside the body. A natural cycle IVF, on the other hand, works with the woman's natural hormonal fluctuations and ovulation cycle.

The history of in vitro fertilisation (IVF) goes back more than half a century. In 1959 the first birth in a nonhuman mammal resulting from IVF occurred, and in 1978 the world's first baby conceived by IVF was born. As medicine advanced, IVF was transformed from natural research to a stimulated clinical treatment. There have been many refinements in the IVF process, and today millions of births have occurred with the help of IVF all over the world.

Induction of final maturation of oocytes is a procedure that is usually performed as part of controlled ovarian hyperstimulation to render the oocytes fully developed and thereby resulting in optimal pregnancy chances. It is basically a replacement for the luteinizing hormone (LH) surge whose effects include final maturation in natural menstrual cycles.

<span class="mw-page-title-main">Use of assisted reproductive technology by LGBT people</span>

Lesbian, gay, bisexual, and transgender people people wishing to have children may use assisted reproductive technology. In recent decades, developmental biologists have been researching and developing techniques to facilitate same-sex reproduction.

References

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  3. ↑ American Cancer Society (2001) Cancer facts and figures 2001. Atlanta: American Cancer Society. Retrieved on April 24, 2007.
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  7. 1 2 Edgar, D. H.; Gook, D. A. (2012). "A critical appraisal of cryopreservation (slow cooling versus vitrification) of human oocytes and embryos". Human Reproduction Update. 18 (5): 536–554. doi:10.1093/humupd/dms016. PMID   22537859.
  8. 1 2 McLaughlin, M; Albertini, D F; Wallace, W H B; Anderson, R A; Telfer, E E (2018). "Metaphase II oocytes from human unilaminar follicles grown in a multi-step culture system" (PDF). MHR: Basic Science of Reproductive Medicine. 24 (3): 135–142. doi: 10.1093/molehr/gay002 . ISSN   1360-9947. PMID   29390119.
    Further comments in BBC News article: James Gallagher (2018-02-09). "First human eggs grown in laboratory". BBC News.
  9. ↑ Magli MC, Lappi M, Ferraretti AP, Capoti A, Ruberti A, Gianaroli L (March 2009). "Impact of oocyte cryopreservation on embryo development". Fertil. Steril. 93 (2): 510–516. doi: 10.1016/j.fertnstert.2009.01.148 . PMID   19342025.
  10. ↑ Practice Committees of the American Society for Reproductive Medicine and the Society for Assisted Reproductive Technology (January 2013). "Mature oocyte cryopreservation: a guideline". Fertility and Sterility. 99 (1): 37–43. doi: 10.1016/j.fertnstert.2012.09.028 . ISSN   1556-5653. PMID   23083924.
  11. ↑ Cil A. P., Bang H., Oktay K. (2013). "Age-specific probability of live birth with oocyte cryopreservation: An individual patient data meta-analysis". Fertility and Sterility. 100 (2): 492–499.e3. doi:10.1016/j.fertnstert.2013.04.023. PMC   3888550 . PMID   23706339.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  12. ↑ Noyes N, Porcu E, Borini A (2009). "With more than 900 babies born, live birth outcomes following oocyte cryopreservation do not appear different from those occurring after conventional IVF". Reprod Biomed Online. 18 (6): 769–776. doi: 10.1016/s1472-6483(10)60025-9 . PMID   19490780.
  13. ↑ CNN April 16, 2007 . Retrieved on April 24, 2007
  14. ↑ ASRM Practice Committee (2009). "ASRM Practice Committee response to Rybak and Lieman: elective self-donation of oocytes". Fertil Steril. 92 (5): 1513–514. doi: 10.1016/j.fertnstert.2009.09.007 . PMID   19836735.
  15. ↑ Glujovsky D, Riestra B, Sueldo C, Fiszbajn G, Repping S, Nodar F, Papier S, Ciapponi A (2014). "Vitrification versus slow freezing for women undergoing oocyte cryopreservation". Cochrane Database of Systematic Reviews. 8 (9): D010047. doi:10.1002/14651858.CD010047.pub2. PMC   11246547 . PMID   25192224.
  16. ↑ Petropanagos, Angel; Cattapan, Alana; Baylis, Françoise; Leader, Arthur (2015-06-16). "Social egg freezing: risk, benefits and other considerations". CMAJ: Canadian Medical Association Journal. 187 (9): 666–669. doi:10.1503/cmaj.141605. ISSN   0820-3946. PMC   4467930 . PMID   25869870.
  17. ↑ "ذخیره «تخمک» برای «مادر شدن» در وقتی دیگر". 17 February 2024.
  18. ↑ Jain, J.; et al. (2005). "Oocyte cryopreservation". Fertility and Sterility. Vol. 86, no. 4. pp. 1037–1046.
  19. ↑ Grifo, J.; Noyes, N. (2010). "Delivery rate using cyropreserved oocytes is comparable to conventional in vitro fertilization using fresh oocytes: potential fertility preservation for female cancer patients". Fertility and Sterility. 93 (2): 391–396. doi: 10.1016/j.fertnstert.2009.02.067 . PMID   19439285.
  20. ↑ Argyle, Catrin E.; Harper, Joyce C.; Davies, Melanie C. (2016-06-01). "Oocyte cryopreservation: where are we now?". Human Reproduction Update. 22 (4): 440–449. doi: 10.1093/humupd/dmw007 . ISSN   1355-4786. PMID   27006004.
  21. ↑ "ASRM Press Release: Fertility Experts Issue New Report on Egg Freezing; ASRM Lifts "Experimental" Label from Technique". www.asrm.org. Retrieved 2017-02-01.
  22. ↑ "Silicon Valley Companies Add New Benefit for Women: Egg-Freezing". NPR.org.
  23. ↑ Henig, Robin Marantz (October 2014). "The Manipulative, Misleading Marketing Campaign to Get Women to Freeze Their Eggs". Slate.
  24. ↑ Brown, Eliza; Patrick, Mary (2018). "Time, Anticipation, and the Life Course: Egg Freezing as Temporarily Disentangling Romance and Reproduction". American Sociological Review. 83 (5): 959–982. doi: 10.1177/0003122418796807 .
  25. ↑ "Department of Defense Press Briefing by Secretary Carter on Force of t". U.S. DEPARTMENT OF DEFENSE. Retrieved 2017-05-01.
  26. ↑ Noyes, N.; Porcu, E.; Borini, A. (2009-06-01). "Over 900 oocyte cryopreservation babies born with no apparent increase in congenital anomalies". Reproductive Biomedicine Online. 18 (6): 769–776. doi: 10.1016/s1472-6483(10)60025-9 . ISSN   1472-6491. PMID   19490780.
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