Ewelina Biskup, M.D. (a, b), Yao Lu, M.D. (c, d), Yun Sun, M.D. (c, d), Mark Trolice, M.D. (e, f), Leslie C. Appiah, M.D. (g), and Steven R. Lindheim, M.D., M.M.M. (c, d, h)
(a) Shanghai University of Medicine and Health Sciences, Shanghai, People’s Republic of China
(b) Department of Internal Medicine, University Hospital of Basel, Basel, Switzerland
(c) Center for Reproductive Medicine, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, People’s Republic of China
(d) Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics, Shanghai, People’s Republic of China
(e) Department of Obstetrics and Gynecology, University of Central Florida College of Medicine, Orlando, Florida
(f) Fertility CARE: The IVF Center, Winter Park, Florida
(g) Department of Obstetrics & Gynecology, The Ohio State University Wexner Medical Center, Columbus, Ohio
(h) Wright State University Boonshoft School of Medicine, Dayton, Ohio
Fertility management across the United States and increasingly world-wide is now an established part of cancer treatment. However, little data exists on fertility preservation for cancer patients in China. With an understanding of the complex social and cultural attitudes, as well as the establishment of evolving guidelines and regulations, the impetus to overcome barriers and to enhance awareness of fertility preservation options for oncofertility patients in China is rapidly moving forward.
As a medical oncologist and a reproductive endocrine infertility specialist, we (EB and SRL) each came as guest physicians, eager to learn, excited to collaborate and energized to educate while working alongside Chinese professionals in the global city of Shanghai. At a local conference, we were asked to speak on health care initiatives from a Western hemisphere perspective. Afterwards, we gravitated toward one another, and as we discovered, had a mutual passion for oncofertility.
According to the 2016 report of the China National Cancer Center there were 12,000 newly diagnosed cancer cases per day in 2015, accounting for a quarter of the global prevalence (1). Furthermore, the incidence has grown 5% within the past 5 years, with nearly 10% of cases in the pre-adolescent, adolescent, and reproductive years. In comparison, an estimated 1,735,350 new cancer cases were diagnosed in the United States in 2018, while approximately 70,000 were adolescent young adults (ages 15-39 years), accounting for about 5 percent of all cancer diagnoses (2). As we learned, this is expected to grow.
While we found with great appreciation how much had been developed and implemented in Shanghai in terms of oncofertility services, a reflection on the progressive Chinese health care system, much was lacking around their utilization. We learned that sperm, oocyte, embryo, and ovarian tissue cryopreservation were available, similar to services provided in the United States and Europe, especially given the application of germ cell cryopreservation initiated in the late 1980s and developed rapidly in the past two decades (3). As an example, the number of oncofertility cases performed in the past five years at one of the leading Chinese teaching hospitals included 270 cases of semen cryopreservation and 14 cases of ovarian tissue cryopreservation, while surprisingly, there was no oocyte or embryo cryopreservation. With respect to semen cryopreservation, comparatively, long-term storage facilities in the United States, including California Cryobank and Fairfax Cryobank, Inc., were contacted directly and stated that in the past 5 years they performed 1,550 and 768 cases of semen cryopreservation for oncofertility, respectively. Reprotech Limited noted their requests for banking increased over 200%. With respect to females, between 2007 and 2017, 420 underwent ovarian tissue cryopreservation at National Physician Cooperatives member institutions of the Oncofertility Consortium under an institutional review board-approved protocol for their own future use or donated 20% of their ovarian tissue to the Oncofertility Consortium-National Physician Cooperatives Repository for research use (4). For oocyte and embryo cryopreservation, according to the 2016 Society of Assisted Reproductive Technology database, there were 87 oocyte and 79 embryo cryopreservation cases, which increased 3.1- and 1.8-fold, respectively to 358 and 221 cases in 2017.
In discussion with our Chinese colleagues, the approach to fertility preservation, might symbolize the Great Wall, where instead of barriers, a growing international communication reinforces collaboration. To Westerners, the Great Wall of China represents a fortification. It was built along an east-to-west line across the historical northern borders of China with the intent to protect the Chinese states and empires against the raids and invasions of various nomadic groups of the Eurasian Steppe. However, the exact opposite is true. The Great Wall embodies a powerful symbol of the unification of China for the first time in the Qin Dynasty (221–206 B.C.) and the ability of the Chinese to work together for the good of the country (5, 6). Moreover, the Great Wall was considered an effective exchange system. It was constructed with beacon towers every few kilometers, from which soldiers communicated in the day by burning wolf dung (as it made a good dense smoke) mixed with different herbs to make colored signal smokes. This provided effective communication if invaders were seen where colored smoke signals were sent up along the wall and reinforcements would be sent to repel the attack. As a result, this signaling was known as colored wolf dung smoke (8).
For oncofertility, one of the obstacles for undergoing preservations is mistaken beliefs and some complex social and cultural attitudes regarding fertility in general and fertility preservation. While not unique to China (a worldwide phenomenon), the misconception of some people is that storage of gamete preservation from an unmarried person is not supported. While true for autologous in vitro fertilization, it is allowed for oncofertility. With respect to sociocultural positions, the importance of opinion among individual family members may also be the source of considerable conflicts, leading to decisions to not pursue fertility preservation and potential family discord, guilt, and long-term regret, which in turn may compromise the cancer patient’s standing in the community. In addition, some individuals with lower health literacy (e.g. rural regions) might assume that oncofertility treatment could increase their risk of recurrence or that the quality of gametes could be reduced after preservation, so that the child’s health might be compromised. This fatalism, where cancer is directly associated with death is still to be found, is not dissimilar to the United States, where fertility preservation remains an afterthought. If there is skepticism from either the partner and/or parents/family, it can lead to situations where the primary focus could be felt to be directed at cancer treatment, “now we have to focus on fighting the cancer and only on that.” Similar to the Great Wall, these well-intentioned family barriers need more updated “colored wolf dung smoke” of knowledge and hope.
To meet this challenge, another “colored wolf dung smoke” has begun to smolder. In 2017, the first program in the Peoples’ Republic of China from the First Affiliated Hospital of Xiamen University in Fujian became a member of the Oncofertility Consortium, adding to the global clinical and research network of 83 institutions in 34 countries. This smoldering intensity is further exemplified, by the recent establishment of The Chinese Fertility Preservation Society to promote fertility preservation research and clinical practice, as well as raise public awareness of fertility preservation and oncofertility, and to provide information, guidelines, access, and resources. Specific clinical regulations in China targeting young female cancer patients is ongoing and currently the American Society of Clinical Oncology guidelines recommend oncologists should inform patients with cancer about potential treatment-related infertility and make appropriate referrals for interested patients (8).
Oncofertility awareness is expected to make strides in physician and public awareness. In the United States, a recent survey by Kohler et al. (9) reported that more than three quarters of physicians and advanced practice nurses in pediatric oncology discussed fertility issues with a high degree of comfort. However, the Western hemisphere faces sex differences in access to fertility-related information and the use of fertility preservation treatment. The impact on fertility is being discussed with adolescent male patients 76% to 100% of the time. Compared to female patients with cancer, males received more information about treatment impact on fertility (80% vs. 48%) and fertility preservation (68% vs. 14%). More than half of men banked frozen sperm whereas only 2% of women underwent fertility preservation (10).
In China, a not so pleasant “herbal scented dung smoke” came from a study by Ju et al. (11) in Fujian, where authors reported that about 20% of reproductive health specialists in this province were not familiar with the term fertility preservation and 30% had never even consulted a cancer patient. It is thus most imperative to equip physicians from rural areas with the knowledge of novel oncofertility services which can help overcoming the consequences of the adverse effects of cancer treatment on reproductive potential.
Currently, level 3 hospitals can provide specialized assisted reproductive technology services. For many patients the distance to specialized, urban centers might pose an enormous barrier and, as a result, most of the level 3 hospitals also offer fellowships for doctors from provinces so that they can be trained and provide oncofertility services locally or refer patients to more specialized centers.
Since our invited guest lectures, we have discussed these aspects with our Chinese colleagues and we agreed that continued awareness and providing accessibility of oncofertility to patients and health care professionals is needed. From patient seminars, professional lectures, to the collaborative creation of Mandarin patient and physician educational materials, the impact has been enormous. In short order, several programs in Shanghai alone have joined the Oncofertility Consortium.
This powerful symbol of unification and the ability to work together is represented by the Great Wall; in the case of oncofertility, by the great “wall” of people who are committed to educating and assisting this growing group of cancer patients. Notwithstanding, barriers still remain, mainly the poor provider and patient awareness about oncofertility. However, China is working extensively on achieving a stronger presence and implementation of fertility preservation. According to the proverb, “要问长城在哪里，就在百姓心坎上。(United we stand — the “Great Wall” is in peoples' hearts), China is moving forward rapidly and is committed to enhancing fertility preservation knowledge and combating misperceptions hindering its practice.
“Nothing happens until something moves.”
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