Can egg freezing technology, with a pregnancy rate of only 4-12%, really achieve reproductive freedom?

Editor’s Note:

At this year's two sessions, the National Health Commission and the All-China Women's Federation jointly submitted a proposal on "supporting the preservation of fertility for older women and female cancer patients." The proposal pointed out that with the development of society and the diversification of personal choices, more and more women choose to marry late or remain single; on the other hand, as the incidence of cancer in my country is on the rise and the survival rate of cancer patients is improving, the protection and preservation of fertility of female cancer patients has gradually received attention, and the demand for fertility preservation is also growing. For a time, "fertility preservation" became the focus of discussion. At present, my country's laws, regulations and medical practices on fertility preservation are still imperfect, especially for the preservation of fertility of older women and cancer patients, there are certain disputes and restrictions. Online public opinion also occasionally discusses the ethics of this technology. However, from a technical perspective, the current fertility preservation can only solve some problems, and the corresponding technology is not fully mature and cannot become everyone's "fertility insurance." The author of this article explains the process and difficulties of fertility preservation. (The preservation method described in the article is a relatively common one. We believe that more advanced methods are being developed and tested, and we look forward to safer and freer technological breakthroughs and applications soon.) We believe that attention to technological development is valuable, and a more objective and rational view of fertility preservation technology will help clarify ideas in discussions.

Technology serves life. In order to help people with difficulties solve fertility problems, many assisted reproductive technologies have been developed. Among them, a large category belongs to fertility preservation , which is mainly for people who have to postpone childbirth for various reasons.

Fertility preservation, as the name suggests, is the preservation of a person's reproductive cells or tissues for future use.

Most of the preservation methods are "cryopreservation", and the frozen objects can be sperm or testicular tissue, eggs or ovarian tissue, or embryos. At present, sperm freezing and embryo freezing technologies are relatively mature, while egg freezing, ovarian tissue freezing, and testicular tissue freezing all have a lot of room for improvement. Among them, egg freezing has always received more attention, and we will talk about the development of related technologies today.

(Photo source: Veer Gallery)

Part 1

How many steps are involved in freezing an egg?

Egg freezing technology involves egg retrieval, freezing, and storage . Since the birth of the first frozen egg baby in 1986, freezing technology has been continuously improved; in 2001, a test-tube baby with vitrified frozen eggs was born; in 2004, a test-tube baby with frozen ovarian tissue was born, and the recovery rate of frozen eggs has been increasing. Since 2013, the American Society for Reproductive Medicine has considered this technology no longer an experimental technology and can be applied clinically.

Why do we need to develop egg freezing technology ? As we mentioned earlier, it is mainly to help some groups preserve their fertility. For example, prepubertal or childbearing female cancer patients before chemotherapy and radiotherapy; women whose ovaries may have been traumatized by surgery; women with genetic reasons, family history of premature ovarian failure, and premature menopause; other women with diseases that affect ovarian function; patients with gene mutations, such as BRCA gene mutations; and women who postpone childbearing due to social pressure and personal wishes.

The process of this technology is not complicated. After evaluating the egg reserves in the ovaries through B-ultrasound and hormone testing, the reproductive doctor determines the superovulation plan and then performs minimally invasive egg retrieval.

After the eggs are retrieved, the quality of each egg, such as maturity, is evaluated under a microscope, and only mature eggs are generally frozen. Next, the eggs are frozen using vitrification technology, and the eggs can be stored in liquid nitrogen for a long time.

At present, vitrification technology is the mainstream of freezing technology . This technology allows the eggs to pass through the ice crystal formation temperature very quickly within 10 seconds, cooling the eggs to the liquid nitrogen temperature. It is called vitrification because during the rapid cooling process, the structure of water after freezing is like glass, rather than the uniform ice crystal structure formed in slow freezing. In addition, compared with slow freezing, vitrification forms fewer ice crystals and causes less damage to the eggs , so the effects of freezing and thawing are relatively good.

The technical process of egg freezing (Source: Public Image)

Several years later, when women who have frozen their eggs are ready to undergo IVF, they will thaw the eggs quickly to avoid damage to the eggs by the ice nuclei. The egg quality will then be assessed under a microscope, and active eggs will be selected for intracytoplasmic sperm injection or in vitro fertilization. The fertilized eggs will then be cultured in vitro for 3 to 5 days before being transplanted into the uterus.

Part 2

Freezing eggs sounds easy but it is difficult to succeed

Although the process is not complicated, there are still many difficulties in egg freezing technology, which is mainly determined by the characteristics of the egg itself.

The egg cell of a mammal is the largest cell in its body , rich in nutrients and genetic material, such as lipids, proteins, nucleic acids, etc., which are all necessary components for early embryonic development. The outer layer of the egg cell is the zona pellucida. Such a cell structure determines that the egg cell is not resistant to freezing, and the survival rate after freezing and thawing is low.

In contrast, the recovery rate of sperm or 3-5 day old embryos after freezing is relatively high, so the related technologies are relatively mature.

Oocyte (Source: Wikipedia)

The changes of egg cells after freezing mainly include: spindle disorder, hardening of zona pellucida, DNA fragmentation, organelle inactivation, parthenogenetic activation, epigenetic modification changes, etc. Therefore, the thawed egg cells observed under a microscope usually show a fragmented internal structure and loss of vitality.

At present, we cannot predict in advance what kind of eggs will have a high recovery rate after freezing. In order to increase the recovery rate of egg cells, they are generally dehydrated with a hypertonic solution.

Moreover, the fertilization rate of thawed eggs is only one-third of that of regular eggs, that is, about 30%, and the embryo implantation rate and live birth rate are much lower than those of regular IVF. In response to these problems, research on cryobiology is currently needed to solve the problem of low egg recovery rate.

In addition, the low utilization rate of frozen eggs by patients is also a problem worthy of attention. Women who need to freeze their eggs should carefully consider the current maturity of the technology and the possibility of using frozen eggs in the future.

In addition to the low survival rate after freezing and thawing, the current pregnancy rate using frozen eggs is only 4-12% , which is still relatively low compared to the 65% pregnancy rate of conventional non-frozen egg IVF technology. The main factors affecting the frozen egg pregnancy rate are the age of the woman when she freezes her eggs and the number of usable eggs after thawing. The younger the age when the eggs are frozen, the better the quality of the eggs. The more usable eggs there are, the more usable embryos will be formed later.

The difficulties of egg freezing technology itself also make people easily raise these questions: Will the length of freezing time affect the eggs? What is the health status of women who give birth through frozen eggs and their children?

According to current data, there is no significant difference between eggs frozen at different times . However, as the egg freezing time increases, the age of the egg owner is also increasing, and the state of their uterus will be affected by age. Older women are not easy to get pregnant, and are more likely to have complications during pregnancy, such as gestational hypertension, diabetes, and dystocia. Many reproductive centers have regulations on the upper age limit for test-tube babies, which is generally around 55 years old in China.

There is no significant difference between children born from frozen eggs and those born from non-frozen eggs . The health risks faced by women who freeze their eggs are basically the same as those who undergo conventional IVF, mainly ovarian hyperstimulation, infection during egg retrieval, bleeding, etc. But don't worry, the incidence of these risks is relatively low, and there are clinical methods for symptomatic treatment.

Part 3

Relatively easy male fertility preservation

For male cancer patients, they can also preserve their fertility by freezing testicular tissue or sperm before radiotherapy and chemotherapy. Compared with female egg retrieval, male sperm retrieval is much easier . For prepubertal boys and other men who cannot obtain sperm, the only way is to obtain testicular tissue through minimally invasive surgery and then freeze it. When young patients reach childbearing age, if there is no available sperm, the previously frozen tissue can be resuscitated and transplanted into the subcutaneous tissue or scrotum to further develop mature sperm, and then offspring can be obtained through assisted reproductive technology.

In 2019, there was a new technological breakthrough in testicular tissue freezing. The Orwig team at the University of Pittsburgh School of Medicine published an article in Science last year: using monkeys as experimental animals, resuscitating and transplanting frozen testicular tissue, and combining assisted reproductive technology to give birth to healthy monkeys. This is a major breakthrough in male fertility preservation, bringing hope to male cancer patients in pre-puberty and childbearing age. The Pittsburgh research team is already recruiting male infertility patients to promote this technology to the clinic as soon as possible.

Monkeys born from testicular tissue freezing technology by Orwig's team (Image source: Orwig)

Part 4

Last words

After birth, people begin to face the problems of growth, development and aging. The essence of fertility preservation technology is, on the one hand, the cold storage technology of biological materials, and on the other hand, the process of people fighting against aging. The situation of having "green mountains" (people are still in childbearing age) but no "firewood" (eggs or sperm quality is not good) often occurs in the population. The current fertility preservation can only solve some problems, and the corresponding technology is not fully mature and cannot become everyone's "fertility insurance" . For example, the freezing recovery rate of eggs and ovarian tissues that we have repeatedly mentioned is very low, and the technology needs to be further improved; humans can make artificial sperm or artificial eggs from animals and clone mice, but these technologies still need years of improvement and ethical discussions before they can be approved for use on humans.

This requires us to correctly assess our needs and living conditions, and to look at fertility preservation technology more objectively and rationally, so that we can make more appropriate choices.

Produced by: Science Popularization China

Produced by: Wei Yubao (Zhengzhou University People's Hospital)

Producer: Computer Network Information Center, Chinese Academy of Sciences

(The images with source indicated in this article have been authorized)

The article only represents the author's views and does not represent the position of China Science Expo

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