Ruan Xiangyan: Guard the source of life and save patients' fertility!

As a female-specific gonadal organ, the ovary plays an important role in nurturing new life and is the source of female life. However, according to data from the World Health Organization's cancer agency, China has more than 4.8 million new cases of malignant tumors each year. With the development of medical technology, the 5-year survival rate of many patients is as high as 90%, and more than 70% of patients have fertility needs. However, radiotherapy and chemotherapy, while improving the survival rate of patients, seriously damage the egg cells of the female ovaries, leading to premature ovarian failure or loss of fertility. According to conservative estimates, there are more than 1 million such people each year.

The ovarian health of contemporary women is full of dangers

Whether the ovaries are healthy can be reflected in many aspects. Professor Ruan Xiangyan of Beijing Obstetrics and Gynecology Hospital affiliated to Capital Medical University said that women can judge the health of their ovaries by their menstrual cycle and menstrual volume. A normal menstrual cycle is 21 to 35 days, the menstrual period is 3 to 7 days, and the menstrual volume is 5 to 80 ml each time. If it exceeds this range, the menstruation is abnormal, indicating that there may be problems with ovarian function. If a woman has a gloomy complexion, often feels weak, and has no energy, it is also a dangerous signal that the health of the ovaries is damaged.

There are many factors that affect ovarian function in daily life. Professor Ruan Xiangyan pointed out that excessive dieting for women can easily induce amenorrhea and premature ovarian failure. Young people have irregular lifestyles, fail to fall asleep during the golden sleep time from 11pm to 3am, and even turn day and night upside down. Vigorous exercise, excessive fitness, and physical exhaustion can also affect ovarian function. In addition, smoking can cause ovarian function to decline one to two years earlier.

Iatrogenic factors can also affect ovarian health, such as radiotherapy and chemotherapy for cancer patients, and bone marrow transplantation, because myeloablative chemotherapy pretreatment before bone marrow transplantation will kill oocytes, leading to premature ovarian failure and affecting female fertility.

How to treat difficult disease: premature ovarian insufficiency

According to the current international and domestic consensus and guidelines, the recognized diagnosis method for premature ovarian insufficiency is irregular menstruation before the age of 40, or amenorrhea for more than 4 months, and the level of follicle-stimulating hormone (FSH) is greater than 25 IU/L for more than 2 consecutive times, with an interval of more than 4 weeks between the 2 measurements. This can lead to a diagnosis of premature ovarian insufficiency.

The cause of premature ovarian insufficiency is relatively complex, and more than half of the patients have no clear cause. Currently known pathogenic factors include chromosomal abnormalities, autoimmune diseases, and iatrogenic injuries. Different treatments are required for different causes. For example, patients with congenital ovarian dysgenesis (Turner syndrome) must protect their fertility in time during childhood, take a part of the ovary and freeze it in vitro, and then transplant the frozen ovarian tissue back into the body when ovarian function declines in the future. This is the most effective prevention and treatment method for patients with Turner syndrome and premature ovarian failure caused by iatrogenic factors. If the patient fails to freeze the ovaries but is diagnosed with premature ovarian failure, the main treatment method is hormone replacement therapy, provided that the patient does not have contraindications such as breast cancer, endometrial cancer, or recent venous thrombosis.

Iatrogenic damage is a major threat to ovarian health. Professor Ruan Xiangyan said, " If cancer cells are compared to walnuts , egg cells are equivalent to grapes. When we use the force of cracking walnuts to kill cancer cells, we will also completely kill egg cells." Therefore, before cancer patients undergo radiotherapy and chemotherapy, doctors have the responsibility to inform patients to protect their fertility and ovarian function. In addition to ovarian cryopreservation and hormone replacement therapy, Chinese medicine or Chinese patent medicine can also be taken as an auxiliary treatment to protect the remaining egg cells. During treatment, nutritional support, moderate exercise, and lifestyle adjustments are indispensable. Premature ovarian insufficiency requires multi-level, individualized comprehensive treatment.

Professor Ruan Xiangyan said: "The technology of ovarian cryopreservation has been successfully carried out in Beijing Obstetrics and Gynecology Hospital. Patients can receive this medical service to prevent premature ovarian failure. Once patients lose the opportunity to cryopreserve their ovaries , whether it is primary or iatrogenic ovarian insufficiency, the treatment opportunities are very limited ."

Professor Ruan Xiangyan's team is committed to fertility preservation and has achieved remarkable results

Ovarian tissue cryopreservation and transplantation first involves removing part of the patient's ovaries before chemotherapy and radiotherapy, and then freezing them. This is equivalent to freezing thousands or even hundreds of thousands of oocytes for the patient. When the patient's primary disease treatment is completed and the body recovers, the frozen ovaries are transplanted back into the patient's body. This can effectively protect the patient's ovarian function and fertility.

Professor Ruan introduced: "Our team has been researching this technology since 2010. After more than ten years of hard work, we successfully achieved the first cryopreserved ovarian tissue transplant in China at Beijing Obstetrics and Gynecology Hospital in 2016. As of 2023, 19 patients have successfully transplanted ovarian tissue, and the Beijing Municipal Health Commission has approved the charging of technical projects related to ovarian tissue cryopreservation and transplantation. The first live birth after cryopreserved ovarian tissue transplantation in 2021 has strongly proved the effectiveness and safety of ovarian tissue cryopreservation."

In 2018, the Beijing Obstetrics and Gynecology Hospital's ovarian tissue cryopreservation and transplantation technology-related project was approved by the Beijing Municipal Health Commission as a "key new medical service price project", marking that this technology has become a routine clinical method to protect the fertility and ovarian endocrine function of Chinese women.

In September 2021, ovarian tissue cryopreservation became a mature technology that can be officially charged for all projects.

As ovarian tissue cryopreservation technology matures and is applied, Professor Ruan Xiangyan hopes that the technology can be included in the national medical insurance so that women with cancer can enjoy the same reproductive rights. To this end, she and her team will continue to move forward and promote this technology nationwide to benefit more patients.

Freezing eggs vs freezing ovaries: the difference is more than just fertility

Freezing eggs and cryopreserving embryos is just a gamble on the probability of fertility. Patients who freeze their eggs need to take ovulation-inducing injections and wait for about two weeks. The waiting time may delay the treatment of the patient's primary disease. For each egg frozen by the patient, the probability of being able to conceive a child in the future is less than 5%. Only by freezing 20 eggs through ovulation induction can there be a chance of live birth in the future . Compared with frozen eggs and frozen embryos, ovarian tissue cryopreservation technology has a better effect on fertility preservation. The number of oocytes it preserves far exceeds that of embryos and eggs. It can also restore the patient's ovarian function to a certain extent, greatly improve the patient's prognosis and quality of life, and protect the fertility of patients with fertility needs. Secondly, frozen ovarian tissue does not need to delay radiotherapy and chemotherapy due to waiting for ovulation induction, and is suitable for girls who have not yet started ovulating. In addition, for women, the ovaries have a very important endocrine function, and after ovarian transplantation, it also plays a very important role in the prevention and treatment of chronic diseases. At present, ovarian tissue cryopreservation is the only way to preserve the fertility of girls.

Professor Ruan introduced that each step of the ovarian tissue cryopreservation technology must be strictly in accordance with the specifications and aseptic operation. The removed ovarian tissue should be placed in the transfer solution immediately. The temperature of the transfer solution should be maintained at 4°C to 8°C. We need to remove the medulla of the ovarian tissue as much as possible, process the ovarian tissue into slices, and balance them in the cryoprotectant solution. Then use the program freezer to gradually cool it to -120°C and store it in a meteorological liquid nitrogen tank. Problems in any of the above operations may lead to the failure of cryopreservation. However, correct operation can preserve the patient's reproductive function for ten or even dozens of years.

Professor Ruan also mentioned: "Breast cancer patients are suitable for cryopreservation technology. Radiotherapy and chemotherapy will destroy their primordial follicles. After the tumor treatment is over, even if menstruation can be restored, only less than 5% of them can become pregnant. However, their uterus is intact and the pregnancy rate after transplantation is also high. Some patients with benign diseases, such as endometriosis, aplastic anemia, and thalassemia, have serious effects on their ovarian function due to bone marrow transplantation and gonadal toxicity treatment, and they also need this technology."

In October 2023, the Fertility Protection and Preservation Professional Committee of the Chinese Association for the Promotion of Human Health Science and Technology and the Beijing Obstetrics and Gynecology Hospital affiliated to Capital Medical University jointly issued the first international group standard "Technical Specifications for Ovarian Tissue Cryopreservation and Transplantation", which stood out among more than 20 group standards in the country and was rated as one of the high-quality group standards of 2023 by the Beijing Standardization Association. In the future, ovarian tissue cryopreservation and transplantation technology can protect the fertility and ovarian function of more girls and women of childbearing age who have lost their fertility and ovarian function due to radiotherapy and chemotherapy, so that they can retain their fertility and ovarian function while receiving radiotherapy and chemotherapy.

Even in the face of wind and rain, light up the fire of life with the bright light

Professor Ruan Xiangyan of Beijing Obstetrics and Gynecology Hospital was selected as an "Expert with Special Government Allowance of the State Council" for her outstanding contributions, and won the "2018 Chinese Scientist of the Year", "Respect Life·2017 Honor Medical Specialist Elite Award", "China Women's Physician Association Lifetime Achievement Award-Five Continents Women's Science and Technology Award", "National Maternal and Child Health Science and Technology Award First Prize for Scientific and Technological Achievements" and "2019 Health Guardian-Tribute to Person Award".

In 2014, due to her international influence, Professor Ruan Xiangyan was elected as a member of the Executive Committee of the International Society of Gynecological Endocrinology, filling a domestic gap, and was re-elected from 2018 to 2022. In 2016, Professor Ruan Xiangyan took the lead in establishing the "Chinese Society of Gynecological Endocrinology of the International Society of Gynecological Endocrinology" and was elected as the chairman. Due to her outstanding contributions in the field of reproductive medicine and obstetrics and gynecology, she was selected into the top 2% of the world's top scientists for two consecutive years in 2021 and 2022!

Professor Ruan Xiangyan often said that life is a racetrack and one cannot give up halfway . In her medical career blueprint, there are more ambitious plans waiting to be implemented. Professor Ruan Xiangyan believes that with the increase in demand, convenient transportation, developed cold chain transportation and policy support, this technology can be carried out nationwide, and patients in need can enjoy the international cutting-edge ovarian tissue cryopreservation technology in their hometown. I hope this technology can become a ray of light at the end of the dark tunnel for young patients!

Professor Ruan Xiangyan