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doi:10.1111/jog.12347
J. Obstet. Gynaecol. Res. Vol. 40, No. 5: 1345–1352, May 2014
Social oocyte freezing: A survey among Singaporean female medical students Shu Qi Tan1, Andy Wei Keat Tan1, Matthew Sie Kuei Lau2, Heng Hao Tan2 and Sadhana Nadarajah2 Departments of 1Obstetrics and Gynaecology and 2Reproductive Medicine, KK Women’s and Children’s Hospital, Singapore, Singapore
Abstract Aim: Social oocyte freezing has gained increasing interest worldwide. We conducted a cross-sectional survey on 129 female medical students in Singapore to assess their mindset and attitudes toward fertility and social oocyte freezing. Methods: An anonymous online survey was conducted among female medical students in Singapore. The desired sample size was 100 participants. Their awareness of the existence of social oocyte freezing was first assessed. An information leaflet was provided subsequently, followed by a more detailed questionnaire. The questions focused on their awareness of age-related fertility decline and their intentions for social oocyte freezing if made available. Results: One hundred and twenty-nine female students participated in the electronic survey, of whom 36.4% had heard of social oocyte freezing. Of these, 70% had personally considered taking up this option. However, after reading the information leaflet, only 48.9% would still consider this option. Of the total, 89.9% considered themselves too old for pregnancy after the age of 35 years, 37.2% would delay family planning for their career, 45.7% would consider social oocyte freezing to postpone family planning for their career, 46.5% would consider oocyte freezing if they had no suitable partners yet, 50.4% may consider freezing their eggs after the age of 30 years and 71.3% may be more amenable to oocyte freezing if government subsidy is available. Conclusion: We hypothesize that social oocyte freezing may be a viable option for single young women who wish to delay child-bearing for ‘reproductive insurance’, so long as this is done with appropriate informed consent with non-directive counseling. Key words: medical students, reproductive insurance, social oocyte freezing, survey.
Introduction Age is a crucial factor in infertility, and reproductive aging is an important social and medical phenomenon. There is an increasing trend for young women to delay their marriage and child-bearing plans in Singapore. This has contributed to the falling local fertility rates. According to the Singapore Department of Statistics, the median age of first marriage for brides rose from
23.6 years in 1980 to 28.0 years in 2011.1 With later marriage, the median age of citizen mothers rose from 28.7 years in 2001 to 29.8 years in 2011.2 Of note, there is a greater proportion of ever-married women in their 30s remaining childless.2 A study by Singh et al. in 1988 looked at the fertility trends in Singapore, and attributed the drop in fertility rate to trends mainly toward higher socioeconomic class such as increasing female labor force participation, a break-up of the extended
Received: August 1 2013. Accepted: November 6 2013. Reprint request to: Dr Shu Qi Tan, Medical Officer, Department of Obstetrics and Gynaecology, KK Women’s and Children’s Hospital, 100 Bukit Timah Road, Singapore 229899. Email: [email protected]
© 2014 The Authors Journal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology
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family system, a rise in the age of first marriage, and more affluent and educated Singaporeans.3 Older women more commonly experience subfertility by the time they are ready to become pregnant. Pregnancy rates decrease exponentially after a maternal age of 37 years, and enter an accelerated decline from age 40–42 years.4 As women start to become aware of the agerelated decline in fertility, interest in the emerging technologies of fertility preservation has grown. Although oocyte and ovarian tissue cryopreservation are commonly considered in women undergoing sterilizing treatment (e.g. chemotherapy, radiation therapy, ovarian resection), social oocyte freezing for women of advancing reproductive age remains controversial. Our study aims to look at the opinion of female medical students on social oocyte freezing to find out its role in our changing society.
Methods The study was targeted at female medical students studying at our local universities (i.e. Yong Loo Lin School of Medicine and Duke-NUS Graduate Medical School). This group of participants was chosen as social oocyte freezing is still an emerging new medical development, and we hypothesize its awareness is higher among this medically inclined group. An online survey via the Google Docs platform was made available to all female medical students over a period of 1 month. The desired sample size was 100, as the primary objective of this study was to have a preliminary assessment of the opinions of medical students on social oocyte freezing. No incentives were given for completion of the survey, and the purpose of the survey was clearly explained to the participants prior to their online participation. The participants’ identities were anonymous, and informed consent was assumed upon submission of the survey forms. The results were subsequently analyzed. This study was reviewed and granted ethical approval by the SingHealth Centralized Institutional Review Board prior to its commencement.
questionnaire. The questions focused on their awareness of age-related fertility decline and their intentions for social oocyte freezing if made available. A copy of the sample information leaflet and questionnaire are attached in the Appendix for reference. The participants’ age ranged 20–31 years old, with a mean age of 23.1 years. The characteristics of the participants are summarized in Table 1. Most of the participants (see Table 2) planned to have their first child between the age of 26 and 30 years, which corresponds to the median age of Singaporean citizen mothers at first birth (29.8 years in 2011).2 On initial assessment, 36.4% (47 students) had heard of social oocyte freezing. Amongst this aware group, 70% (33 students) would personally consider taking up this option before reading the information leaflet. However, only 48.9% (23 students) of these still considered social oocyte freezing after reading the information leaflet (see Fig. 1). All the respondents were asked a second time if they would opt for social oocyte freezing after the initial assessment. Of the 129 respondents, 26.4% answered ‘yes’, 19.4% answered ‘no’, and 54.3% answered ‘I do not know’. Table 1 Characteristics of survey participants n Age, years 30 Race Chinese Malay Indian Other Religion Buddhist Catholic Christian Muslim Hinduism Other
%
2 91 35 1
1.6 70.5 27.1 0.8
116 2 9 2
89.9 1.55 7.0 1.55
27 8 43 4 3 44
21.0 6.2 33.3 3.1 2.3 34.1
Results The online survey was made available over a period of 1 month in September 2012 to all female medical students studying in our local universities. One hundred and twenty-nine participants took part in the survey. Their awareness of the existence of social oocyte freezing was first assessed. An information leaflet was provided subsequently, followed by a more detailed
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Table 2 At what age do you plan to have your first child? Age, years
n (%)
21–25 26–30 31–35 36–39 >40
1 (0.8) 73 (64.3) 42 (32.6) 1 (0.8) 2 (1.6)
© 2014 The Authors Journal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology
Social oocyte freezing
Table 3 Reasons for considering oocyte freezing Will you consider oocyte freezing
Yes
No
Total
(a) if you have no suitable partner yet? (b) to focus on career and postpone family planning?
60 (46.5%) 59 (45.7%)
69 (53.5%) 70 (54.3%)
129 (100%) 129 (100%)
Table 4 Subanalysis of reasons for considering oocyte freezing If no suitable partner Yes No To focus on career and postpone family building
Yes No
40 (31.0%) 20 (15.5%)
19 (14.7%) 50 (38.8%)
Table 5 Timing of oocyte freezing
Figure 1 Awareness of social oocyte freezing and uptake.
On assessment of timing for pregnancy and relation to career, 69.0% of the respondents considered themselves too old for pregnancy after the age of 35 years, and 37.2% of the respondents would delay family building for their career. The reasons for considering social oocyte freezing were explored (see Table 3), with 45.7% willing to consider social oocyte freezing to postpone family planning for their career and 46.5% of respondents willing to consider oocyte freezing if they had no suitable partners yet. Although 31.0% of the respondents would consider social oocyte freezing for both reasons, 14.7% would only consider this option to delay family building for career reasons, while 15.5% would consider this option solely if they had no available partner (see Table 4). The timing of uptake of social oocyte freezing was discussed. Most respondents (50.4%) felt that they may consider freezing their eggs after the age of 30 years (see Table 5) and 30% of the students felt that oocyte freezing should be made available to women up to the age of 45 years. With regards to cost of oocyte freezing, 34.1% felt that payment for this elective procedure should be entirely borne by the patient (see Fig. 2). However,
What age will you freeze your oocytes?
n
%
21–25 years 26–30 years 31–35 years 36–40 years >40 years Total
16 48 49 9 7 129
12.4 37.2 38.0 7.0 5.4 100
should government subsidy be made available, 71.3% (92 students) of the respondents may be more amenable to oocyte freezing.
Discussion Our survey revealed some important points about social oocyte freezing. First, only 36.4% of our medical students are aware of the availability of this procedure. Given the assumption that medical students should have better knowledge of the current new medical developments, this highlights the need to create greater public awareness before this procedure can be offered to the general public. Accurate information on the details regarding social oocyte freezing also should be made available to the general public for it to be a viable option. Our study noted that of the students who are aware of the procedure, there was a sharp decline in the percentage (from 70% to 48.9%) who would personally consider taking up social oocyte freezing after reading the information leaflet, which discussed the success rates of oocyte freezing, the procedure for oocyte retrieval, as well as the cost of the procedure. The importance of providing
© 2014 The Authors Journal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology
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Figure 2 Who should pay for social oocyte freezing?
adequate information to the patients who consider social oocyte freezing is paramount given the many implications involved: medical, social and emotional. Medical implications need to be spelt out for proper informed consent for the procedure, as this may sway decisions made by the patients. The timeframe for social oocyte freezing is also crucial. Of our respondents, 50.4% felt that they may consider oocyte freezing after the age of 30 years. Reasons cited include delaying family planning for career reasons, and lack of a suitable partner. Such reasons are not limited to the medical field. Many other professionals may face a similar dilemma with increasing age. The natural history of fecundity as well as success rates with older cryopreservation particularly should be highlighted to secure the best age timeframe for social freezers. Our survey group targeted a young population mainly in the age range of 21–24 years. At the time of study, they may not have not felt the pressure of their ticking biological clock. However, it is important to raise awareness among young women. The average reported age of non-medical patients freezing their oocytes is 38 years.5–8 Research has shown that freezing above 43 years is not recommended with pregnancy rates per cycle of 2% and lower.9 In our survey, 30% of our medical students felt that it should be made available to women up to the age of 45 years. This suggests that there is a big gap that needs to be filled to improve the public’s knowledge on the truth about social oocyte freezing. Women should be adequately advised on the
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improved embryo quality and reduced prevalence of aneuploid oocytes with younger age. One common argument raised against social oocyte freezing is the probable resultant delay in age of marriage and childbirth for women. This is a notable concern, as our survey reflects that nearly half of our respondents would consider oocyte freezing to focus on their career. However, it is important to note that one of the other important reasons to consider oocyte freezing is the lack of a suitable partner. The various reasons for uptake of social oocyte freezing should be considered, and explored by clinicians to facilitate effective counseling for this elective procedure. Overall, only 26.4% of our surveyed population would eventually opt for social oocyte freezing, while 54.3% were unsure. This trend is also reflected in a similar online survey performed by the Bioethics Legal group for Reproductive Issues in Singapore (BELRIS)10 to evaluate the position of Singaporean women on oocyte freezing in Singapore. In BELRIS’s survey, only 22% of respondents stated that they are likely to opt for elective oocyte freezing, and 47% were unsure. Interestingly, the Singaporean attitudes toward oocyte freezing reflect a stark contrast to results shown in a Belgium survey conducted by Stoop et al.11 The Belgium group had only 3.1% of the respondents who would consider freezing their oocytes, while 45.1% were unsure and 51.8% answered no. This difference is not attributed to knowledge about social oocyte freezing. Stoop et al.11 reported that women who consider oocyte freezing did not appear to have better awareness of reproductive aging. Possible explanations for this difference could be cultural and societal mindset. Stoop et al.11 suggested that their group of potential oocyte freezers had a greater desire for more children, as this option would possibly prolong their reproductive years. This may not be relevant to our population, where a local study found a statistically significant trend for the younger population to have no intention for children.12 The desire for ‘reproductive insurance’ seems to be the main contributing factor in our Singaporean population, where the most selected reason by potential freezers in the BELRIS10 study was to have a ‘safety net’ in case of future reproductive problems. Our results reflect a similar trend for need for reproductive insurance, where most respondents may consider oocyte freezing after the age of 30 years should they remain childless, keeping in mind that the majority of our respondents planned to have their first child between the ages 26 of 30 years.
© 2014 The Authors Journal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology
Social oocyte freezing
Given that reproductive insurance is a major reason for local women to favor social oocyte freezing, it is paramount that the successful clinical pregnancy rates are dutifully presented. It must be emphasized that oocyte freezing may retain the chance of being a genetic parent. However, there is no guarantee that a live birth will result. Such information must be properly translated to the public prior to uptake of the procedure to prevent misconceptions. Nevertheless, this option of reproductive insurance has a huge price tag. Social oocyte freezing is currently prohibited in Singapore. By extrapolating the current government policies to funding of this elective procedure, the cost is still quite hefty. Nearly one third of our respondents (34.1%) felt that payment for this elective procedure should be paid entirely by the patients. However, the uptake rate may increase to 71.3% should government subsidy be made applicable to this procedure. This is important for the government making policies as the trend to postpone childbearing plans for the sake of a career has increased in the local setting over recent years. Given the expensive nature of this elective procedure, working out the payment issues for this particular group of competitive working women may influence their decision for social oocyte freezing. Our survey targeted a focused competitive population which is more likely to uptake social oocyte freezing for career reasons, and we took advantage of their medical knowledge to evaluate the role of oocyte freezing in our Singaporean society. It has highlighted a few key points. First, public awareness and knowledge about social oocyte freezing is inadequate. With appropriate informed consent and non-directive counseling, social oocyte freezing may be a viable option for women who wish to obtain this reproductive insurance. In addition, women are likely to be more amendable to take up the procedure if government funding is made available. This may be useful for policy makers to consider when implementing government policies and allocation of budget.
Acknowledgments We would like to thank our female medical students at Yong Loo Lin School of Medicine and Duke-NUS Graduate Medical School for their kind participation in the survey. We would also like to thank Dr Ku Chee Wai for his kind assistance with setting up the online survey via the Google Docs platform.
Disclosure None
References 1. Singapore Department of Statistics. Demographic Indicators, 1970–2012. 2012. 2. Singapore Department of Statistic. Population in Brief 2012. 2012. 3. Singh K, Viegas O, Ratnam SS. Fertility trends in Singapore. J Biosoc Sci 1988; 20: 401–409. 4. Committee on Gynecologic Practice of American College of Obstetricians and Gynecologists; Practice Committee of American Society for Reproductive Medicine. Age-related fertility decline: A committee opinion. Fertil Steril 2008; 90 (5 Suppl): S154–S155. 5. Gold E, Copperman K, Witkin G, Jones C, Capperman AB. P-187: A motivational assessment of women undergoing elective egg freezing for fertility preservation. Fertil Steril 2006; 86: S201. 6. Klein J, Howard M, Grunfeld L, Mukherjee T, Sandler B, Copperman AB. P-486: Preliminary experience of an oocyte cryopreservation of an oocyte cryopreservation program: Are patients presenting too late? Fertil Steril 2006; 86: S315. 7. Sage CFF, Kolb BM, Treiser SL, Silverberg KM, Barrit J, Copperman AB. Oocyte cryopreservation in women seeking elective fertility preservation – a multicenter analysis. Obstet Gynecol 2008; 111: 20S. 8. Nekkebroeck J, Stoop D, Devroey P. O-036 a preliminary profile of women opting for oocyte crypreservation for nonmedical reasons. Hum Reprod 2010; 25: 1l5–1l6. 9. Hourvitz A, Machtinger R, Maman E et al. Assisted reproduction in women over 40 years of age: How old is too old?, Reprod Biomed Online 2009; 19: 599–603. 10. BELRIS. Report on Survey Conducted to Evaluate the Position of Elective Oocyte Freezing in Singapore. Newsletter [Cited 2013.] Available from URL: http://belris.sg/wp -content/uploads/2013/06/BELRIS-NEWSLETTER_Q2 _2013.pdf 11. Stoop D, Nekkebroeck J, Devroey P. A survey on the intentions and attitudes toward oocyte cryopreservation for medical reasons among women of reproductive age. Hum Reprod 2011; 26: 655–661. 12. Tan TC, Tan SQ, Wei X. Cross-sectional pregnancy survey on fertility trends and pregnancy knowledge in Singapore. J Obstet Gynaecol Res 2011; 37: 992–996.
Appendix I Social oocytes freezing: to do or not to do? 1. What is your race? ○ Chinese ○ Malay ○ Indian ○ Others (please specify:________) 2. What is your age? _______ 3. What is your religion? ○ Buddhist ○ Muslim ○ Christian ○ Hinduism
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4. 5. 6. 7.
8.
9.
10. 11.
○ Catholic ○ Non-religious ○ Others (pls specify:_______) Do you plan to have children? ○ Yes ○ No At what age do you plan to have your first child? ○ 21–25 ○ 26–30 ○ 31–35 ○ 36–39 ○ >40 Will you delay family planning for your career? ○ Yes ○ No If so, are you worried about impaired fertility due to advanced age? ○ Yes ○ No When do you consider yourself too old to get pregnant? ○ >21 ○ >26 ○ >31 ○ >35 ○ >40 Would you consider freezing your oocytes at some point in time? ○ Yes ○ No ○ I do not know At what age would you consider oocyte freezing? ○ 21–25 ○ 26–30 ○ 31–35 ○ 36–39 ○ >40 Would you consider oocyte freezing if you have no suitable partner yet? ○ Yes ○ No
12. Would you consider oocyte freezing to focus on your career and postpone family planning? ○ Yes ○ No 13. Who should pay for the oocytes freezing? ○ Self – Cash ○ Medisave ○ Government-Subsidy 14. If there is government subsidy available for oocyte freezing, would you be more amendable to freezing your eggs? ○ Yes ○ No 15. What do you think is the upper age limit for pregnancy? i.e. when is it not acceptable for a woman to get pregnant? ○ >45 ○ >50 ○ >55 ○ >60 16. Do you think social oocytes freezing should be offered to woman in all ages? ○ Yes ○ No If no, which age group should egg freezing be made available to? ○ 31–35 ○ 31 39 ○ 31–45
Appendix II PARTICIPANT INFORMATION SHEET
Protocol Title: Social Oocyte freezing: To do or not to do? A survey amongst Singapore female medical students. Principal Investigator(s): Dr Tan Wei Keat, Medical Officer, KK Women’s and Children’s Hospital Dr Tan Shu Qi, Medical Officer, KK Women’s and Children’s Hospital PURPOSE OF THE RESEARCH STUDY You are being invited to participate in a cross sectional study to find out the role of social oocyte freezing in our local population. There is increasing trend for young women to delay their childbearing plans till later in their reproductive years. This is largely attributed to postgraduate academic pursuit and higher levels of professional achievement. Studies have shown a trend for young women to delay their child bearing age. However, the ability to conceive is strongly influenced by a woman’s age. Older women more commonly experience subfertility by the time they are ready to become pregnant. As many women started to become aware of the age-related decline in fertility, interest in the emerging technologies of fertility preservation has grown. Our study aims to look at societal opinions on social oocyte freezing to halt the effects of time on reproductive function.
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© 2014 The Authors Journal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology
Social oocyte freezing
NATURAL FECUNDITY Fecundity refers to the ability to reproduce. The fertility of a woman is mainly influenced by her age. The progressive loss of oocytes that occurs from fetal life until menopause is one of the defining features of the age-related decline in female fertility. The oocyte pool peaks at birth. Subsequently, progressive atresia occurs, and happens at an accelerated rate after the age of 37 in normal women till menopause. As the number of oocytes declines over time, the quality of oocytes also declines, resulting in an increased prevalence of aneuploid oocytes due to dysfunctions of the meiotic spindle. Studies have consistently demonstrated a decline in pregnancy rates with advancing maternal age, with higher rates of miscarriage among older women. These relationships are best illustrated by outcome data from clinics performing in vitro fertilization. With age-relate decreasing fecundity coupled with the delay in childbearing age in modern society, Leridon et al.1 have shown that this has resulted in an up to 73% increase in need for fertility treatments. IVF PREGNANCY RATES The most important factor by far when assessing pregnancy outcomes in IVF cycles is female age. More oocytes can be harvested with improved live birth rates in the younger patients. Results at our KK IVF centre based on 2008 data are summarized as shown.
Mean no of oocytes collected Mean no of embryos formed Live Birth Rates (fresh cycle)
40
21.1 12.5 43.4%
15.8 9.5 43.5%
13.4 7.6 26.3%
9.8 5.2 9.0%
INFORMATION ABOUT OOCYTE FREEZING The first successful pregnancy from oocyte cryopreservation was reported in 1986. However, oocyte freezing is still regarded as a relatively experimental procedure by most major regulatory bodies in the United States and Europe, particularly for social indications. This is due to concerns about the procedure’s success rates and safety for future offspring. However, with improving techniques like vitrification for oocyte freezing, there is an increasing trend for social oocyte freezing, especially in ladies who are postponing childbirth to a later age. For women who do not have a participating male partner and are not interested in using donor sperm, oocyte cryopreservation is generally the preferred option until a suitable partner is found. OOCYTE FREEZING Traditionally, oocytes are frozen via slow freeze method, but with poor outcomes. Vitrification is a relatively new approach to oocyte freezing. The first reported live birth from vitrified human oocytes was in 1999. It is based upon the principle that metabolically active cells can be cooled so rapidly that ice does not have time to form. Successful use of vitrification procedures has been reported in animal models, and the number of human live births resulting from vitrification of oocytes is encouraging. Several case series showing promising results have been published. A meta-analysis including five reports on vitrification estimated fertilization rates of 74 percent (637/859), clinical pregnancy rates per transfer of 45.5 percent (61/134), and live birth rate per transfer of 36.6 percent (49/134). A study comparing fresh and vitrified oocytes shows comparable embryo quality, pregnancy rates and implantation potential for both arms.2 The data is summarized the table below.
© 2014 The Authors Journal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology
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Oocyte survival rates (%) Fertilization rate (%) No of resultant embryos Pregnancy rate per embryo transfer (%) Live birth rate (%)
Fresh
Frozen (Vitrified)
P value
NA 86.6 5 ± 0.27 48.8 41.5%
91.4% 84.4 4.3 ± 0.23 55.6 47.2%
NA 0.50 0.08 0.55 0.61
PROCEDURE Potential candidates will generally undergo baseline ovarian reserve testing prior to initiating treatment. The processes of embryo and oocyte cryopreservation are identical to that of in vitro fertilization up until the time of the oocyte retrieval. Controlled ovarian hyperstimulation with daily injectable gonadotropins is initiated in the early follicular phase or after an interval on the birth control pills, and continues for approximately 10 to 14 days to achieve multiple peri-ovulatory follicles. The oocyte retrieval is performed via needle aspiration utilizing transvaginal ultrasound guidance, typically under conscious sedation. Mature oocytes retrieved are frozen on the day of the oocyte retrieval. For sufficient oocyte collection (usually about 20 oocytes), 3 cycles of oocyte stimulation and retrival are usually required. COST The cost of embryo and oocyte cryopreservation procedures is comparable to that of in vitro fertilization. A single cycle including monitoring visits, surgical, anaesthesia and embryology is approximately $8000. For 3 cycles, the cost is estimated at $24 000. Annual storage fees are approximately $400 per year. LONG TERM FOLLOW UP OF CHILDREN There is limited data on the long term follow up of children for oocyte vitrification techniques. In the largest study, Chian et al.3 (2008) reported data on 200 children. The mean birth weight was 2920 grams for singletons and 2231 grams for multiples. The low birth weight rate among singletons was 18% and among multiples 80%. The premature delivery rate was 26% for singletons and 71% for multiple pregnancies. The incidence of congenital malformations was 2.5%. A review by Wennerholm et al.4 revealed a total of 221 successful infants born via this technique, but there is no long term child follow up data for cryopreservation techniques as of now. CONCLUSION Vitrification of oocytes promises to be an effective method of fertility preservation for women. We would like to gauge the opinion of future professional women, such as yourself, on fertility preservation with oocyte cryopreservation. Thank you for taking the time to participate in our survey.
1 Leridon H, Slama R, The impact of a decline in fecundity and of pregnancy postponement on final number of children and demand on assisted reproduction technology, Human Repro, 2008; 23:1312–19. 2 Trokoudes KM, Pavlides C, Zhang X, Comparison outcome of fresh and vitrified donor oocytes in an egg-sharing donation program, Fert Stert, 2011; 95: 1996–2000. 3 Chian RC, Huang JY, Gilbert L et al., Obstetric outcomes following vitrification of in-vitro and in vivo matured oocytes, Fertil Steril, 2008. 4 Wennerholm UB, Soderstrom-Anttila V, Bergh C et al., Children born after cryopreservation of embryos or ooctes: a systematic review of outcome data, Human Repro, 2009; 24: 2158–72.
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doi:10.1111/jog.12347
J. Obstet. Gynaecol. Res. Vol. 40, No. 5: 1345–1352, May 2014
Social oocyte freezing: A survey among Singaporean female medical students Shu Qi Tan1, Andy Wei Keat Tan1, Matthew Sie Kuei Lau2, Heng Hao Tan2 and Sadhana Nadarajah2 Departments of 1Obstetrics and Gynaecology and 2Reproductive Medicine, KK Women’s and Children’s Hospital, Singapore, Singapore
Abstract Aim: Social oocyte freezing has gained increasing interest worldwide. We conducted a cross-sectional survey on 129 female medical students in Singapore to assess their mindset and attitudes toward fertility and social oocyte freezing. Methods: An anonymous online survey was conducted among female medical students in Singapore. The desired sample size was 100 participants. Their awareness of the existence of social oocyte freezing was first assessed. An information leaflet was provided subsequently, followed by a more detailed questionnaire. The questions focused on their awareness of age-related fertility decline and their intentions for social oocyte freezing if made available. Results: One hundred and twenty-nine female students participated in the electronic survey, of whom 36.4% had heard of social oocyte freezing. Of these, 70% had personally considered taking up this option. However, after reading the information leaflet, only 48.9% would still consider this option. Of the total, 89.9% considered themselves too old for pregnancy after the age of 35 years, 37.2% would delay family planning for their career, 45.7% would consider social oocyte freezing to postpone family planning for their career, 46.5% would consider oocyte freezing if they had no suitable partners yet, 50.4% may consider freezing their eggs after the age of 30 years and 71.3% may be more amenable to oocyte freezing if government subsidy is available. Conclusion: We hypothesize that social oocyte freezing may be a viable option for single young women who wish to delay child-bearing for ‘reproductive insurance’, so long as this is done with appropriate informed consent with non-directive counseling. Key words: medical students, reproductive insurance, social oocyte freezing, survey.
Introduction Age is a crucial factor in infertility, and reproductive aging is an important social and medical phenomenon. There is an increasing trend for young women to delay their marriage and child-bearing plans in Singapore. This has contributed to the falling local fertility rates. According to the Singapore Department of Statistics, the median age of first marriage for brides rose from
23.6 years in 1980 to 28.0 years in 2011.1 With later marriage, the median age of citizen mothers rose from 28.7 years in 2001 to 29.8 years in 2011.2 Of note, there is a greater proportion of ever-married women in their 30s remaining childless.2 A study by Singh et al. in 1988 looked at the fertility trends in Singapore, and attributed the drop in fertility rate to trends mainly toward higher socioeconomic class such as increasing female labor force participation, a break-up of the extended
Received: August 1 2013. Accepted: November 6 2013. Reprint request to: Dr Shu Qi Tan, Medical Officer, Department of Obstetrics and Gynaecology, KK Women’s and Children’s Hospital, 100 Bukit Timah Road, Singapore 229899. Email: [email protected]
© 2014 The Authors Journal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology
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family system, a rise in the age of first marriage, and more affluent and educated Singaporeans.3 Older women more commonly experience subfertility by the time they are ready to become pregnant. Pregnancy rates decrease exponentially after a maternal age of 37 years, and enter an accelerated decline from age 40–42 years.4 As women start to become aware of the agerelated decline in fertility, interest in the emerging technologies of fertility preservation has grown. Although oocyte and ovarian tissue cryopreservation are commonly considered in women undergoing sterilizing treatment (e.g. chemotherapy, radiation therapy, ovarian resection), social oocyte freezing for women of advancing reproductive age remains controversial. Our study aims to look at the opinion of female medical students on social oocyte freezing to find out its role in our changing society.
Methods The study was targeted at female medical students studying at our local universities (i.e. Yong Loo Lin School of Medicine and Duke-NUS Graduate Medical School). This group of participants was chosen as social oocyte freezing is still an emerging new medical development, and we hypothesize its awareness is higher among this medically inclined group. An online survey via the Google Docs platform was made available to all female medical students over a period of 1 month. The desired sample size was 100, as the primary objective of this study was to have a preliminary assessment of the opinions of medical students on social oocyte freezing. No incentives were given for completion of the survey, and the purpose of the survey was clearly explained to the participants prior to their online participation. The participants’ identities were anonymous, and informed consent was assumed upon submission of the survey forms. The results were subsequently analyzed. This study was reviewed and granted ethical approval by the SingHealth Centralized Institutional Review Board prior to its commencement.
questionnaire. The questions focused on their awareness of age-related fertility decline and their intentions for social oocyte freezing if made available. A copy of the sample information leaflet and questionnaire are attached in the Appendix for reference. The participants’ age ranged 20–31 years old, with a mean age of 23.1 years. The characteristics of the participants are summarized in Table 1. Most of the participants (see Table 2) planned to have their first child between the age of 26 and 30 years, which corresponds to the median age of Singaporean citizen mothers at first birth (29.8 years in 2011).2 On initial assessment, 36.4% (47 students) had heard of social oocyte freezing. Amongst this aware group, 70% (33 students) would personally consider taking up this option before reading the information leaflet. However, only 48.9% (23 students) of these still considered social oocyte freezing after reading the information leaflet (see Fig. 1). All the respondents were asked a second time if they would opt for social oocyte freezing after the initial assessment. Of the 129 respondents, 26.4% answered ‘yes’, 19.4% answered ‘no’, and 54.3% answered ‘I do not know’. Table 1 Characteristics of survey participants n Age, years 30 Race Chinese Malay Indian Other Religion Buddhist Catholic Christian Muslim Hinduism Other
%
2 91 35 1
1.6 70.5 27.1 0.8
116 2 9 2
89.9 1.55 7.0 1.55
27 8 43 4 3 44
21.0 6.2 33.3 3.1 2.3 34.1
Results The online survey was made available over a period of 1 month in September 2012 to all female medical students studying in our local universities. One hundred and twenty-nine participants took part in the survey. Their awareness of the existence of social oocyte freezing was first assessed. An information leaflet was provided subsequently, followed by a more detailed
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Table 2 At what age do you plan to have your first child? Age, years
n (%)
21–25 26–30 31–35 36–39 >40
1 (0.8) 73 (64.3) 42 (32.6) 1 (0.8) 2 (1.6)
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Table 3 Reasons for considering oocyte freezing Will you consider oocyte freezing
Yes
No
Total
(a) if you have no suitable partner yet? (b) to focus on career and postpone family planning?
60 (46.5%) 59 (45.7%)
69 (53.5%) 70 (54.3%)
129 (100%) 129 (100%)
Table 4 Subanalysis of reasons for considering oocyte freezing If no suitable partner Yes No To focus on career and postpone family building
Yes No
40 (31.0%) 20 (15.5%)
19 (14.7%) 50 (38.8%)
Table 5 Timing of oocyte freezing
Figure 1 Awareness of social oocyte freezing and uptake.
On assessment of timing for pregnancy and relation to career, 69.0% of the respondents considered themselves too old for pregnancy after the age of 35 years, and 37.2% of the respondents would delay family building for their career. The reasons for considering social oocyte freezing were explored (see Table 3), with 45.7% willing to consider social oocyte freezing to postpone family planning for their career and 46.5% of respondents willing to consider oocyte freezing if they had no suitable partners yet. Although 31.0% of the respondents would consider social oocyte freezing for both reasons, 14.7% would only consider this option to delay family building for career reasons, while 15.5% would consider this option solely if they had no available partner (see Table 4). The timing of uptake of social oocyte freezing was discussed. Most respondents (50.4%) felt that they may consider freezing their eggs after the age of 30 years (see Table 5) and 30% of the students felt that oocyte freezing should be made available to women up to the age of 45 years. With regards to cost of oocyte freezing, 34.1% felt that payment for this elective procedure should be entirely borne by the patient (see Fig. 2). However,
What age will you freeze your oocytes?
n
%
21–25 years 26–30 years 31–35 years 36–40 years >40 years Total
16 48 49 9 7 129
12.4 37.2 38.0 7.0 5.4 100
should government subsidy be made available, 71.3% (92 students) of the respondents may be more amenable to oocyte freezing.
Discussion Our survey revealed some important points about social oocyte freezing. First, only 36.4% of our medical students are aware of the availability of this procedure. Given the assumption that medical students should have better knowledge of the current new medical developments, this highlights the need to create greater public awareness before this procedure can be offered to the general public. Accurate information on the details regarding social oocyte freezing also should be made available to the general public for it to be a viable option. Our study noted that of the students who are aware of the procedure, there was a sharp decline in the percentage (from 70% to 48.9%) who would personally consider taking up social oocyte freezing after reading the information leaflet, which discussed the success rates of oocyte freezing, the procedure for oocyte retrieval, as well as the cost of the procedure. The importance of providing
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Figure 2 Who should pay for social oocyte freezing?
adequate information to the patients who consider social oocyte freezing is paramount given the many implications involved: medical, social and emotional. Medical implications need to be spelt out for proper informed consent for the procedure, as this may sway decisions made by the patients. The timeframe for social oocyte freezing is also crucial. Of our respondents, 50.4% felt that they may consider oocyte freezing after the age of 30 years. Reasons cited include delaying family planning for career reasons, and lack of a suitable partner. Such reasons are not limited to the medical field. Many other professionals may face a similar dilemma with increasing age. The natural history of fecundity as well as success rates with older cryopreservation particularly should be highlighted to secure the best age timeframe for social freezers. Our survey group targeted a young population mainly in the age range of 21–24 years. At the time of study, they may not have not felt the pressure of their ticking biological clock. However, it is important to raise awareness among young women. The average reported age of non-medical patients freezing their oocytes is 38 years.5–8 Research has shown that freezing above 43 years is not recommended with pregnancy rates per cycle of 2% and lower.9 In our survey, 30% of our medical students felt that it should be made available to women up to the age of 45 years. This suggests that there is a big gap that needs to be filled to improve the public’s knowledge on the truth about social oocyte freezing. Women should be adequately advised on the
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improved embryo quality and reduced prevalence of aneuploid oocytes with younger age. One common argument raised against social oocyte freezing is the probable resultant delay in age of marriage and childbirth for women. This is a notable concern, as our survey reflects that nearly half of our respondents would consider oocyte freezing to focus on their career. However, it is important to note that one of the other important reasons to consider oocyte freezing is the lack of a suitable partner. The various reasons for uptake of social oocyte freezing should be considered, and explored by clinicians to facilitate effective counseling for this elective procedure. Overall, only 26.4% of our surveyed population would eventually opt for social oocyte freezing, while 54.3% were unsure. This trend is also reflected in a similar online survey performed by the Bioethics Legal group for Reproductive Issues in Singapore (BELRIS)10 to evaluate the position of Singaporean women on oocyte freezing in Singapore. In BELRIS’s survey, only 22% of respondents stated that they are likely to opt for elective oocyte freezing, and 47% were unsure. Interestingly, the Singaporean attitudes toward oocyte freezing reflect a stark contrast to results shown in a Belgium survey conducted by Stoop et al.11 The Belgium group had only 3.1% of the respondents who would consider freezing their oocytes, while 45.1% were unsure and 51.8% answered no. This difference is not attributed to knowledge about social oocyte freezing. Stoop et al.11 reported that women who consider oocyte freezing did not appear to have better awareness of reproductive aging. Possible explanations for this difference could be cultural and societal mindset. Stoop et al.11 suggested that their group of potential oocyte freezers had a greater desire for more children, as this option would possibly prolong their reproductive years. This may not be relevant to our population, where a local study found a statistically significant trend for the younger population to have no intention for children.12 The desire for ‘reproductive insurance’ seems to be the main contributing factor in our Singaporean population, where the most selected reason by potential freezers in the BELRIS10 study was to have a ‘safety net’ in case of future reproductive problems. Our results reflect a similar trend for need for reproductive insurance, where most respondents may consider oocyte freezing after the age of 30 years should they remain childless, keeping in mind that the majority of our respondents planned to have their first child between the ages 26 of 30 years.
© 2014 The Authors Journal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology
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Given that reproductive insurance is a major reason for local women to favor social oocyte freezing, it is paramount that the successful clinical pregnancy rates are dutifully presented. It must be emphasized that oocyte freezing may retain the chance of being a genetic parent. However, there is no guarantee that a live birth will result. Such information must be properly translated to the public prior to uptake of the procedure to prevent misconceptions. Nevertheless, this option of reproductive insurance has a huge price tag. Social oocyte freezing is currently prohibited in Singapore. By extrapolating the current government policies to funding of this elective procedure, the cost is still quite hefty. Nearly one third of our respondents (34.1%) felt that payment for this elective procedure should be paid entirely by the patients. However, the uptake rate may increase to 71.3% should government subsidy be made applicable to this procedure. This is important for the government making policies as the trend to postpone childbearing plans for the sake of a career has increased in the local setting over recent years. Given the expensive nature of this elective procedure, working out the payment issues for this particular group of competitive working women may influence their decision for social oocyte freezing. Our survey targeted a focused competitive population which is more likely to uptake social oocyte freezing for career reasons, and we took advantage of their medical knowledge to evaluate the role of oocyte freezing in our Singaporean society. It has highlighted a few key points. First, public awareness and knowledge about social oocyte freezing is inadequate. With appropriate informed consent and non-directive counseling, social oocyte freezing may be a viable option for women who wish to obtain this reproductive insurance. In addition, women are likely to be more amendable to take up the procedure if government funding is made available. This may be useful for policy makers to consider when implementing government policies and allocation of budget.
Acknowledgments We would like to thank our female medical students at Yong Loo Lin School of Medicine and Duke-NUS Graduate Medical School for their kind participation in the survey. We would also like to thank Dr Ku Chee Wai for his kind assistance with setting up the online survey via the Google Docs platform.
Disclosure None
References 1. Singapore Department of Statistics. Demographic Indicators, 1970–2012. 2012. 2. Singapore Department of Statistic. Population in Brief 2012. 2012. 3. Singh K, Viegas O, Ratnam SS. Fertility trends in Singapore. J Biosoc Sci 1988; 20: 401–409. 4. Committee on Gynecologic Practice of American College of Obstetricians and Gynecologists; Practice Committee of American Society for Reproductive Medicine. Age-related fertility decline: A committee opinion. Fertil Steril 2008; 90 (5 Suppl): S154–S155. 5. Gold E, Copperman K, Witkin G, Jones C, Capperman AB. P-187: A motivational assessment of women undergoing elective egg freezing for fertility preservation. Fertil Steril 2006; 86: S201. 6. Klein J, Howard M, Grunfeld L, Mukherjee T, Sandler B, Copperman AB. P-486: Preliminary experience of an oocyte cryopreservation of an oocyte cryopreservation program: Are patients presenting too late? Fertil Steril 2006; 86: S315. 7. Sage CFF, Kolb BM, Treiser SL, Silverberg KM, Barrit J, Copperman AB. Oocyte cryopreservation in women seeking elective fertility preservation – a multicenter analysis. Obstet Gynecol 2008; 111: 20S. 8. Nekkebroeck J, Stoop D, Devroey P. O-036 a preliminary profile of women opting for oocyte crypreservation for nonmedical reasons. Hum Reprod 2010; 25: 1l5–1l6. 9. Hourvitz A, Machtinger R, Maman E et al. Assisted reproduction in women over 40 years of age: How old is too old?, Reprod Biomed Online 2009; 19: 599–603. 10. BELRIS. Report on Survey Conducted to Evaluate the Position of Elective Oocyte Freezing in Singapore. Newsletter [Cited 2013.] Available from URL: http://belris.sg/wp -content/uploads/2013/06/BELRIS-NEWSLETTER_Q2 _2013.pdf 11. Stoop D, Nekkebroeck J, Devroey P. A survey on the intentions and attitudes toward oocyte cryopreservation for medical reasons among women of reproductive age. Hum Reprod 2011; 26: 655–661. 12. Tan TC, Tan SQ, Wei X. Cross-sectional pregnancy survey on fertility trends and pregnancy knowledge in Singapore. J Obstet Gynaecol Res 2011; 37: 992–996.
Appendix I Social oocytes freezing: to do or not to do? 1. What is your race? ○ Chinese ○ Malay ○ Indian ○ Others (please specify:________) 2. What is your age? _______ 3. What is your religion? ○ Buddhist ○ Muslim ○ Christian ○ Hinduism
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4. 5. 6. 7.
8.
9.
10. 11.
○ Catholic ○ Non-religious ○ Others (pls specify:_______) Do you plan to have children? ○ Yes ○ No At what age do you plan to have your first child? ○ 21–25 ○ 26–30 ○ 31–35 ○ 36–39 ○ >40 Will you delay family planning for your career? ○ Yes ○ No If so, are you worried about impaired fertility due to advanced age? ○ Yes ○ No When do you consider yourself too old to get pregnant? ○ >21 ○ >26 ○ >31 ○ >35 ○ >40 Would you consider freezing your oocytes at some point in time? ○ Yes ○ No ○ I do not know At what age would you consider oocyte freezing? ○ 21–25 ○ 26–30 ○ 31–35 ○ 36–39 ○ >40 Would you consider oocyte freezing if you have no suitable partner yet? ○ Yes ○ No
12. Would you consider oocyte freezing to focus on your career and postpone family planning? ○ Yes ○ No 13. Who should pay for the oocytes freezing? ○ Self – Cash ○ Medisave ○ Government-Subsidy 14. If there is government subsidy available for oocyte freezing, would you be more amendable to freezing your eggs? ○ Yes ○ No 15. What do you think is the upper age limit for pregnancy? i.e. when is it not acceptable for a woman to get pregnant? ○ >45 ○ >50 ○ >55 ○ >60 16. Do you think social oocytes freezing should be offered to woman in all ages? ○ Yes ○ No If no, which age group should egg freezing be made available to? ○ 31–35 ○ 31 39 ○ 31–45
Appendix II PARTICIPANT INFORMATION SHEET
Protocol Title: Social Oocyte freezing: To do or not to do? A survey amongst Singapore female medical students. Principal Investigator(s): Dr Tan Wei Keat, Medical Officer, KK Women’s and Children’s Hospital Dr Tan Shu Qi, Medical Officer, KK Women’s and Children’s Hospital PURPOSE OF THE RESEARCH STUDY You are being invited to participate in a cross sectional study to find out the role of social oocyte freezing in our local population. There is increasing trend for young women to delay their childbearing plans till later in their reproductive years. This is largely attributed to postgraduate academic pursuit and higher levels of professional achievement. Studies have shown a trend for young women to delay their child bearing age. However, the ability to conceive is strongly influenced by a woman’s age. Older women more commonly experience subfertility by the time they are ready to become pregnant. As many women started to become aware of the age-related decline in fertility, interest in the emerging technologies of fertility preservation has grown. Our study aims to look at societal opinions on social oocyte freezing to halt the effects of time on reproductive function.
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NATURAL FECUNDITY Fecundity refers to the ability to reproduce. The fertility of a woman is mainly influenced by her age. The progressive loss of oocytes that occurs from fetal life until menopause is one of the defining features of the age-related decline in female fertility. The oocyte pool peaks at birth. Subsequently, progressive atresia occurs, and happens at an accelerated rate after the age of 37 in normal women till menopause. As the number of oocytes declines over time, the quality of oocytes also declines, resulting in an increased prevalence of aneuploid oocytes due to dysfunctions of the meiotic spindle. Studies have consistently demonstrated a decline in pregnancy rates with advancing maternal age, with higher rates of miscarriage among older women. These relationships are best illustrated by outcome data from clinics performing in vitro fertilization. With age-relate decreasing fecundity coupled with the delay in childbearing age in modern society, Leridon et al.1 have shown that this has resulted in an up to 73% increase in need for fertility treatments. IVF PREGNANCY RATES The most important factor by far when assessing pregnancy outcomes in IVF cycles is female age. More oocytes can be harvested with improved live birth rates in the younger patients. Results at our KK IVF centre based on 2008 data are summarized as shown.
Mean no of oocytes collected Mean no of embryos formed Live Birth Rates (fresh cycle)
40
21.1 12.5 43.4%
15.8 9.5 43.5%
13.4 7.6 26.3%
9.8 5.2 9.0%
INFORMATION ABOUT OOCYTE FREEZING The first successful pregnancy from oocyte cryopreservation was reported in 1986. However, oocyte freezing is still regarded as a relatively experimental procedure by most major regulatory bodies in the United States and Europe, particularly for social indications. This is due to concerns about the procedure’s success rates and safety for future offspring. However, with improving techniques like vitrification for oocyte freezing, there is an increasing trend for social oocyte freezing, especially in ladies who are postponing childbirth to a later age. For women who do not have a participating male partner and are not interested in using donor sperm, oocyte cryopreservation is generally the preferred option until a suitable partner is found. OOCYTE FREEZING Traditionally, oocytes are frozen via slow freeze method, but with poor outcomes. Vitrification is a relatively new approach to oocyte freezing. The first reported live birth from vitrified human oocytes was in 1999. It is based upon the principle that metabolically active cells can be cooled so rapidly that ice does not have time to form. Successful use of vitrification procedures has been reported in animal models, and the number of human live births resulting from vitrification of oocytes is encouraging. Several case series showing promising results have been published. A meta-analysis including five reports on vitrification estimated fertilization rates of 74 percent (637/859), clinical pregnancy rates per transfer of 45.5 percent (61/134), and live birth rate per transfer of 36.6 percent (49/134). A study comparing fresh and vitrified oocytes shows comparable embryo quality, pregnancy rates and implantation potential for both arms.2 The data is summarized the table below.
© 2014 The Authors Journal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology
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Oocyte survival rates (%) Fertilization rate (%) No of resultant embryos Pregnancy rate per embryo transfer (%) Live birth rate (%)
Fresh
Frozen (Vitrified)
P value
NA 86.6 5 ± 0.27 48.8 41.5%
91.4% 84.4 4.3 ± 0.23 55.6 47.2%
NA 0.50 0.08 0.55 0.61
PROCEDURE Potential candidates will generally undergo baseline ovarian reserve testing prior to initiating treatment. The processes of embryo and oocyte cryopreservation are identical to that of in vitro fertilization up until the time of the oocyte retrieval. Controlled ovarian hyperstimulation with daily injectable gonadotropins is initiated in the early follicular phase or after an interval on the birth control pills, and continues for approximately 10 to 14 days to achieve multiple peri-ovulatory follicles. The oocyte retrieval is performed via needle aspiration utilizing transvaginal ultrasound guidance, typically under conscious sedation. Mature oocytes retrieved are frozen on the day of the oocyte retrieval. For sufficient oocyte collection (usually about 20 oocytes), 3 cycles of oocyte stimulation and retrival are usually required. COST The cost of embryo and oocyte cryopreservation procedures is comparable to that of in vitro fertilization. A single cycle including monitoring visits, surgical, anaesthesia and embryology is approximately $8000. For 3 cycles, the cost is estimated at $24 000. Annual storage fees are approximately $400 per year. LONG TERM FOLLOW UP OF CHILDREN There is limited data on the long term follow up of children for oocyte vitrification techniques. In the largest study, Chian et al.3 (2008) reported data on 200 children. The mean birth weight was 2920 grams for singletons and 2231 grams for multiples. The low birth weight rate among singletons was 18% and among multiples 80%. The premature delivery rate was 26% for singletons and 71% for multiple pregnancies. The incidence of congenital malformations was 2.5%. A review by Wennerholm et al.4 revealed a total of 221 successful infants born via this technique, but there is no long term child follow up data for cryopreservation techniques as of now. CONCLUSION Vitrification of oocytes promises to be an effective method of fertility preservation for women. We would like to gauge the opinion of future professional women, such as yourself, on fertility preservation with oocyte cryopreservation. Thank you for taking the time to participate in our survey.
1 Leridon H, Slama R, The impact of a decline in fecundity and of pregnancy postponement on final number of children and demand on assisted reproduction technology, Human Repro, 2008; 23:1312–19. 2 Trokoudes KM, Pavlides C, Zhang X, Comparison outcome of fresh and vitrified donor oocytes in an egg-sharing donation program, Fert Stert, 2011; 95: 1996–2000. 3 Chian RC, Huang JY, Gilbert L et al., Obstetric outcomes following vitrification of in-vitro and in vivo matured oocytes, Fertil Steril, 2008. 4 Wennerholm UB, Soderstrom-Anttila V, Bergh C et al., Children born after cryopreservation of embryos or ooctes: a systematic review of outcome data, Human Repro, 2009; 24: 2158–72.
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