Why can't prices remain high?, A test tube baby costs 30000 to 50000 yuan in time | Test tube baby | remains high

After undergoing artificial insemination and three IVF surgeries, Liu Yan gave birth to a daughter, which took more than two years. "I feel a sense of relief now. It's really not easy along the way. Giving birth may be easy for some people, but it's difficult for others."

As one of the most effective methods for treating infertility, assisted reproduction has promising future development prospects in the context of encouraging fertility policies. According to the Sullivan report, the size of China's assisted reproductive market was 43.4 billion yuan in 2020, and it is expected that the size of China's assisted reproductive market will reach 85.4 billion yuan by 2025.

To increase the penetration rate of assisted reproduction in China, the price is still an unavoidable issue. For example, having a test tube baby requires a cost of 30000 to 50000 yuan. The success rate of in vitro fertilization is not 100%, and some people need to undergo several cycles, which increases the cost.

Currently, the door to medical insurance reimbursement is gradually opening up to the assisted reproductive industry. The inclusion of assisted reproductive technology in medical insurance can solve some of the financial burdens on patients.

Assisted reproduction that is gradually being included in medical insurance

Starting from July 1st this year, Beijing officially included 16 therapeutic assisted reproductive technology projects in the payment scope of medical insurance and work-related injury insurance in Beijing.

It is reported that these 16 therapeutic assisted reproductive technology projects include ovulation induction testing, sperm selection and treatment, sperm selection and treatment - density gradient centrifugation, intrauterine artificial insemination, etc., covering artificial insemination and related technologies of first, second, and third generation IVF, with most of them included in Class A medical insurance.

Similarly, starting from July 1st, Liaoning Province will also include 18 assisted reproductive projects such as embryo culture and embryo transfer in the maternity insurance directory.

The market has long called for the inclusion of assisted reproduction in medical insurance, and the national level is also releasing signals.

In September 2021, the National Medical Insurance Administration stated for the first time that in terms of diagnosis and treatment projects, it will guide various regions, based on the positioning of "basic insurance", and gradually incorporate mature, safe, reliable, and cost controllable therapeutic assisted reproductive technologies that medical insurance can afford into the scope of medical insurance payment according to procedures on the basis of scientific calculation and sufficient argumentation.

In February of this year, the National Medical Insurance Administration issued a response letter to the proposal to include infertility treatment in free medical care, stating that suitable childbirth analgesia and assisted reproductive technology projects will gradually be included in the payment scope of the medical insurance fund.

Assisted reproductive technology mainly refers to the use of medical techniques and methods to artificially manipulate gametes, zygotes, and embryos in order to achieve the purpose of conception. It mainly includes artificial fertilization technology, in vitro fertilization embryo transfer technology, the latter also known as "in vitro fertilization technology", which is the most widely used.

On July 25, 1978, the world's first test tube baby was born in the UK. On March 10, 1988, the first test tube baby in Chinese Mainland was born in the Department of Obstetrics and Gynecology, Peking University Third Hospital.

Over the past few decades, in vitro fertilization (IVF) technology has evolved from the first generation to the third generation. The first generation refers to conventional in vitro fertilization (IVF) technology, which starts from the egg to solve the problem of female infertility; The second generation refers to the technology of intracytoplasmic sperm microinjection, which is artificially selected by embryologists for fertilization, mainly solving the problem of male infertility; The third generation refers to genetic diagnosis technology before embryo implantation, which is based on first and second generation technology and can screen embryos without chromosomal or genetic diseases for implantation. All three generations of technology have been approved for use in China.

Different technologies result in different treatment cycle costs. According to a research report by Southwest Securities, the cost for both the first and second generations is 30000 yuan, while the cost for the third generation can reach as high as 50000 to 100000 yuan.

Starting from May to June 2020, I started undergoing examinations and attempted artificial insemination in September, but failed. In October, I switched to IVF and began preparing for various preoperative examinations until January 2021 when I underwent my first egg retrieval surgery. It took more than 2 years from starting assisted reproduction to giving birth. At that time, I traveled back and forth to the hospital. My personal feeling is that finding a reliable hospital and doctor is important, but there are still a few good hospitals and doctors at present. People who need IVF technology generally have a strong desire to conceive, but the overall treatment cost is not cheap. Taking us as an example, the cumulative cost of three times is more than 100000 yuan. If there is some subsidy, I think it will motivate them. "More people with infertility are trying assisted reproduction," said Liu Yan.

"A test tube baby cycle starts with treatment and only counts as one cycle after the embryo is inserted into the uterus. The cost of this cycle is generally between 30000 and 50000 yuan, which is indeed a considerable expense. If it is included in medical insurance, it can reduce some costs, which can benefit economically disadvantaged families. However, it remains to be seen whether more people will try test tube babies after being included in medical insurance, because the success rate of test tube babies is still subject to various factors, such as the physical conditions of both men and women," said Liu Yanhui, director of the Reproductive Center of Luohu District People's Hospital in Shenzhen, in an interview with First Financial News.

IVF is expensive

A complete IVF technology needs to go through stages such as ovarian stimulation, egg extraction, egg fertilization, embryo development, embryo selection, embryo transfer, pregnancy testing, and baby birth.

The success rate of IVF therapy can be defined by clinical pregnancy rate or live birth rate. The clinical pregnancy rate is calculated by dividing the number of clinical pregnancies by the number of embryo transfers, while the live birth rate is calculated by dividing the number of births that lead to live births by the number of embryo transfers. Although these two indicators are widely used in the United States, clinical pregnancy rates are more commonly used in China.

Even today, in vitro fertilization technology is not 100% successful. Data shows that the current global assisted reproductive live birth rate is less than 40%, and a successful IVF typically requires 2 to 3 incubation cycles. Therefore, multiple cultivation also means higher costs.

"Of course, we hope to succeed in one cultivation cycle, but different families have different etiologies. The probability of success in one cultivation cycle is not very high. According to my estimation, this probability is about 30%, which is related to specific populations, such as younger individuals who may have a success rate of 40% to 50%. The older the age, the lower the probability of success. For those over 40 years old, the probability of success in one cultivation cycle is very low, and they may need to do two to three cycles, or even five cycles, and the related costs are also skyrocketing. Overall, 2-3 cycles of cultivation account for the majority." Liu Yanhui said.

In the process of in vitro fertilization, most of the medical devices used are imported, which to some extent leads to higher overall treatment costs.

"If imported consumables are used, the cost of assisted reproduction will be relatively higher. Currently, most domestic assisted reproductive culture products are monopolized by foreign products." Professor Jin Lei from Tongji Hospital affiliated with Tongji Medical College of Huazhong University of Science and Technology told a reporter from First Financial News that if assisted reproductive medical devices can be localized, it will help reduce the treatment cost of assisted reproduction.

Southwest Securities stated in its research report that the cost of assisted reproduction is currently high, with surgical treatment accounting for a relatively large proportion. In each step of the assisted reproductive therapy cycle, various categories of medical devices are involved, which can be roughly divided into liquid and operational products according to their nature. Liquid products mainly include products such as semen retrieval, egg retrieval, culture, transplantation, and biopsy fluid involved in the steps of egg retrieval, gamete processing, and culture. Operational products include surgical instruments and professional equipment such as egg retrieval needles, microinjection needles, embryo transfer catheters, culture dishes, microinjection microscopes, and embryo culture boxes.

Due to the direct impact of related devices on the success rate of assisted reproductive surgery, regulatory authorities in China have strict regulations on devices, slow evaluation processes, and high technical difficulties in products. Currently, foreign manufacturers with earlier development and more mature technology are still the main focus, such as Vitrolife from Sweden, Cook from the United States, Wallace from the United Kingdom, ORIGIO from Denmark, and other manufacturers occupying a large market share.

According to a spokesperson from an assisted reproductive medical institution, a typical IVF technology cycle costs between 30000 and 50000 yuan, with drug consumables accounting for up to 30% of the total cost.

Domestic medical devices are gradually being replaced

The most basic and critical requirement of assisted reproductive technology is to obtain the highest quality embryos and perform embryo transfer. The impact of embryo culture medium on embryo quality is crucial.

"Embryo culture medium is a crucial step in our 'production' of offspring," said Jin Lei.

In the entire process of assisted reproduction, embryo culture medium plays an indispensable role as a "food and clothing parent". The first few days of each test tube baby's life are spent in the embryo culture laboratory, from gametes to fertilized cleavage embryos and blastocysts, and the entire process is "roaming" in the culture medium. During the process of embryonic development in vitro, the culture medium simulates the internal environment in which the embryo develops in the mother's body, providing it with air, water, and food for growth, while alleviating external damage to the embryo. Therefore, embryo nutrient solution is also known as the first "divine water" for embryonic babies.

"In recent years, domestically produced assisted reproductive technology products, including domestic culture media, have also been developing rapidly," said Jin Lei.

Public information shows that the domestic embryo culture medium market has always been dominated by Vitrolife from Sweden and Cook from the United States. It is worth mentioning that Cook's embryo culture medium sold domestically is actually licensed from Genea Biomedx in Singapore.

On May 15th this year, domestic company Beikang Medical announced a $40 million acquisition of BMX and its seven subsidiaries.

After the completion of this acquisition, Beikang Medical plans to bring BMX's third-generation full line culture medium into the Chinese market.

"Embryo incubators and culture media are very scarce embryo laboratory resources in China. In the future, we will bring higher quality and lower price products to China's assisted reproductive industry through localized production." Yin Lejun, CFO of Beikang Medical, said at the Genea Biomedx New Product Greater China Conference and the strategic cooperation signing ceremony between Beikang Medical and Genea Group recently held.

In addition, data from the National Medical Products Administration shows that some domestic enterprises such as Weituo Biotechnology, Aiweifu, Ails, and Dongyun Medical have been approved for their culture medium products.

"For embryo culture medium, we value product stability. The culture medium should be co cultured with eggs, sperm, and embryos for a long time to promote embryonic development and ultimately produce healthy offspring. In this process, the stability of the culture medium is very important, and it needs to be ensured that it does not change due to environmental temperature, light, gas, and other factors within its validity period." Jin Lei said.

Liu Yanhui said that if domestic embryo culture media is to be replaced, it will take time, and the acceptance by clinical doctors also requires a process.

"It is necessary to first verify in a small-scale culture room, gain experience, and then slowly spread it out." Jin Lei said that almost all domestic enterprises have been involved in the reagents related to the culture room, but few can be involved in all products. He hopes that in the future, domestic enterprises can establish a full product chain and provide one-stop products and solutions around the assisted reproductive laboratory. For example, starting from washing sperm in the culture room, processing egg cells, insemination, embryo culture, blastocyst culture, freezing to recovery, all products from the same manufacturer can be used. This can avoid possible interference between products from different manufacturers.

Domestic substitution of medical devices has been a hot topic in the industry in recent years, and the country has also introduced a series of supporting policies to actively promote it. According to the process of domestic substitution of medical devices, domestic substitution of medical devices can be divided into four states: import monopoly, accelerated substitution, equal competition, and domestic advantage. In the industry's view, domestic assisted reproductive medical devices are currently undergoing accelerated replacement.

The barriers to assisted reproductive industry remain high

Recently, at the 2023 Assisted Reproduction Seminar initiated by the Shenzhen Medical Device Industry Association, Zhang Xiaoyong, Executive General Manager of the Investment Banking Department of China International Finance Co., Ltd., believed that the three core driving factors of China's assisted reproductive market include infertility patients, penetration rate, and per capita cost.

In his view, the phenomenon of late marriage and late pregnancy is becoming increasingly prominent, and policies encouraging childbirth have also contributed to the demand for assisted reproduction. At the same time, the number of infertility cases in China is on the rise year by year. In terms of assisted reproductive penetration rate, there is still a considerable gap compared to overseas markets in China, but it is rapidly increasing, including the following three dimensions: China's egg retrieval cycle is rapidly increasing, and penetration rate is expected to be close to that of the United States; Compared to Japan and the United States, the proportion of in vitro fertilization births in China is relatively low; Assisted reproduction accelerates its inclusion in medical insurance, greatly reducing patient burden and increasing penetration rate.

It is worth noting that the barriers to entry for the entire assisted reproductive service industry remain high. To some extent, the high cost of assisted reproduction is also related to high industry barriers.

Southwest Securities stated in its research report that currently, the number of assisted reproductive service institutions in China is still relatively small, and the overall market is mainly dominated by public hospitals, with a dispersed competition pattern and market concentration. The assisted reproductive industry also relies heavily on doctors, and it is still in the early stages of development in China. The number of experienced medical staff is limited, which also limits the speed of enterprise expansion.

"License, doctor, and technology form three core barriers." Southwest Securities stated that China's assisted reproductive institution license is set at one institution per 3 million population. Compared to the US market, China's assisted reproductive market has strict policy barriers, strict license approval standards, long processes, and higher physical requirements for patients. As of the end of June 2020, there were a total of 523 medical institutions approved for the development of human assisted reproductive technology in China, and 27 medical institutions for human sperm banks.

With the development of social economy, adjustment of population policies, and changes in people's reproductive concepts and lifestyles, the fertility rate has been decreasing year by year, and the age of female fertility has been continuously delayed. Infertility has become one of the major reproductive diseases that troubles many couples of childbearing age, and assisted reproductive technology is considered one of the most effective methods for treating infertility.

According to the latest survey and analysis results of national reproductive health epidemiology released by Qiao Jie, an academician team from Peking University Third Hospital, the incidence rate of infertility in China has risen from 12% to 18% between 2007 and 2020.

"The first test tube baby in the world was born in 1978, and the first test tube baby in Chinese Mainland was born in 1988. In more than 30 years, assisted reproductive technology in Chinese Mainland has developed rapidly. At present, the total cycle number has exceeded 1 million cycles/year, and the number of babies born has exceeded 300000 cases/year. The power generation has basically approached the level of developed countries in Europe and the United States." said the team of academicians Qiao Jie.

It is reported that with the rapid development of single-cell whole genome sequencing technology and gene function research, Chinese scientists have made remarkable progress in exploring the molecular mechanisms of gametogenesis and early embryonic development, providing effective diagnostic and therapeutic methods for certain genetic or rare diseases, including new pre implantation genetic diagnostic methods for single gene diseases and chromosomal translocations.

"Although we developed more than a decade later than abroad, our domestic business volume is relatively large, and our technology in various aspects is no less than that of Western countries, and we can even surpass it," Liu Yanhui told a reporter from First Financial News.

However, Jin Lei told First Financial reporters that there are still bottlenecks to be overcome in the field of assisted reproductive technology.

In the embryo culture room, the most important step is how to select a good embryo. The embryo is a type of cell. Although we have a set of judgment criteria for embryos at all levels, this is not 100% perfect. There is still room for improvement in how to select a good embryo. In addition, in basic research, further research is needed on how the embryo interacts with the endometrium. Some embryos look good and the endometrium looks good, but even if the embryo is placed inside, it cannot be conceived. On the contrary, some people can conceive embryos and endometrium with average quality. The reasons behind this may be related to the ability of the endometrium to receive embryos. However, research on this aspect is still ongoing. "It's quite lacking," Jin Lei said.

*Liu Yan is a pseudonym in the text