INTRODUCTION The use of complementary and alternative medicine (CAM) is generally increasing. CAM use in relation to fertility treatment is sparsely studied. Thus, the aim of this study was to assess the use prevalence and patterns of CAM among Danish women and men initiating or receiving fertility treatment. Additionally, we aimed to establish whether several fertility treatment attempts influenced CAM use prevalence.
METHODS A cross-sectional survey was conducted at the second largest fertility clinic in Denmark in the period from April to June 2018. The CAM use prevalence was reported for two groups of patients. Specifically, CAM use prior to or during fertility treatment was compared between groups, and various general patterns were reported.
RESULTS Among the 411 patients approached, 277 responded (67.4%). Among these patients, 142 participants had not previously received fertility treatment, whereas 135 participants had received treatment at least once previously. We found that 52.5% of the patients initiating and undergoing fertility treatment had used CAM. Furthermore, previous fertility treatment was related to a higher CAM use. Surprisingly, only 53.4% of the participating women used folic acid.
CONCLUSIONS More than half of the women and men initiating or undergoing fertility treatment had been using the investigated CAM. Of notice, folic acid compliance was low. The frequency of CAM use increased during fertility treatment.
TRIAL REGISTRATION not relevant.
Complementary and alternative medicine (CAM) is used worldwide for a variety of purposes. Studies have shown that the global use of herbal medicine has increased among specific patient groups, including patients with cardiovascular and rheumatic diseases, pregnant and menopausal women and patients with psychological diseases [1-5]. Some patients use CAM to prevent disease; others to benefit from the treatment or to avoid unsatisfactory effects of conventional treatments . However, this area has only been sparsely studied and more research into the effect of CAM in general and in relation to fertility treatment in particular is needed .
CAM comprises a variety of different types of vitamins, minerals and other supplements. Folic acid is the only recommended supplement before and during pregnancy, partly because it prevents birth defects, partly because it improves the chance of achieving and maintaining a pregnancy . Use of other CAM and herbal medicines during pregnancy has been studied only sparsely, and some types of CAM have been identified as being potentially harmful . Thus, the purpose of this study was to assess the prevalence and patterns of CAM use among Danish women and men initiating or receiving fertility treatment. Additionally, the study evaluated whether several fertility treatment attempts influenced the prevalence of CAM use.
Study setting and participants
All women and men referred for in vitro fertilisation (IVF) treatment in the second largest Danish public fertility clinic at Horsens Regional Hospital from April to June 2018 were invited to attend a general information meeting prior to their first fertility treatment. Furthermore, for two weeks, all women and men visiting the outpatient clinic for a treatment appointment - e.g., their second stimulation - were invited to participate. The only exclusion criterion was language challenges as non-Danish speaking patients may not be able to complete the survey independently.
A cross-sectional survey was conducted to evaluate the use prevalence of complementary vitamins, minerals, herbs and alternative treatment. The definition of CAM varies in the literature. In this study, we defined CAM as follows: vitamins and minerals, omega-3 fatty acids, herbs and alternative treatment. Herbs comprised St. John’s Wort, valerian, ginger, kava, ginseng, pomegranate and others. Alternative treatment comprised reflexology, acupuncture, craniosacral therapy, massage, mindfulness and osteopathy. The survey consisted of questions concerning demographic characteristics, fertility treatment and information about CAM. Demographic characteristics including age, gender, level of education, occupational status and civil status were also obtained.
Data collection and statistical analysis
Data were collected in RedCap - a secure web application for building and managing surveys with proper and safe information processing ensuring anonymity.
Statistical analyses were performed in EpiBasic - a tool for statistical analysis of tabular information. The χ2-test was used for comparison of the use prevalence of vitamins, minerals, herbs and alternative treatment between the two groups of patients prior to or during fertility treatment. A p-value < 0.05 was considered statistically significant.
Trial registration: not relevant.
In total, 411 women and men were invited to participate. Among those invited, 277 participants accepted and were enrolled in the study, yielding a 67.4% total response rate. Among the enrolled patients, 243 were seen in relation to their first referral for fertility treatment, and 168 of the women and men were seen while attending the outpatient clinic. In total, 251 women and men were invited for the information meeting of whom 125 consented to participating. In the outpatient clinic, 160 women and men were invited and 152 consented to participating.
The demographics of the studied groups are presented in Table 1. In total, 277 patients participated, 191 women and 86 men. Among the 277 participants, 142 had not previously received fertility treatment (51.3%, 96 women and 46 men), whereas 135 had received at least one treatment (48.7%).
The age distribution within the two studied groups was nearly identical with most of the participants being 25-34 years of age in both groups. The only significant difference was that the group of participants who had not previously received fertility treatment had a significantly higher proportion of participants aged 30-34 years (p < 0.05) than participants who had received fertility treatment previously. Regarding level of education, most participants in the two study groups had an education lasting three to four and a half years, or a minimum of five years. The majority were in a relationship and employed.
Overall use of complementary and alternative medicine
Overall, 52.5% (n = 145) of women and men reported using vitamins, minerals, herbs and/or alternative treatment. The use prevalence was significantly higher among women than among men; 78.6% (n = 114) and 21.4% (n = 31), respectively (p < 0.02).
Use of vitamins and minerals
The use of vitamins and minerals is presented in Table 2. The prevalence in the two groups ranged from 7.8% to 45.2% depending on the types of vitamins and minerals used. In general, the use prevalence of vitamins and minerals was higher among participants who had previously received fertility treatment than among participants initiating fertility treatment, although this difference did not reach statistical significance. The only exception was vitamin A (Table 2).
Folic acid was reported by 53.4% (n = 102) of all women. The prevalence was higher among women who had previously received fertility treatment (59.4%) than among women initiating fertility treatment (47.4%), but this difference was not significantly significant (p = 0.10).
Use of herbs
The use prevalence of herbs was significantly higher among participants who had previously received fertility treatment (20.8%, n = 28) than among participants who had never received fertility treatment (9.2%, n = 13), (p < 0.04). Furthermore, the use was higher among women (15.7%, n = 30) than among men (10.9%, n = 9), but this difference was not statistically significant (p = 0.25). The most frequently used herb was ginger. Thus, 4.2% (n = 6) of the participants who had not received fertility treatment previously and 8.2% (n = 11) of the participants who had received fertility treatment previously used ginger (p = 0.17).
Use of alternative treatment
A total of 27.4% (n = 37) of the participants who had previously received fertility treatment used alternative treatment. This percentage was significantly higher than the 16.9% (n = 29, p < 0.049) of the participants who had not received fertility treatment previously (Table 3). Again, women used alternative treatment significantly more frequently (29.8%, n = 57) than men (3.5%, n = 3, p < 0.001). Depending on the type of alternative treatment, we found that the use prevalence of each type ranged from 0.7% to 17.8%, with acupuncture being the most used treatment. For details, see Table 3. Statistical analyses were conducted (Table 3), but the low prevalence in this group should be taken into account when interpreting these results.
Pattern in the use of complementary and alternative medicine
When investigating the CAM use prevalence stratified by level of education, we compared participants having primary school as the highest attained educational level to participants with high school, an education lasting two years, 3-4.5 years or a minimum of five years. We found an increasing use prevalence with a higher level of education (from around 2% to 50%). The only exception was participants who had an education lasting a minimum of five years, among whom only an average of 25% used CAM.
No difference was observed in the CAM use prevalence when exploring civil status, occupational status or age groups.
To our knowledge, this is the first study to investigate the use of CAM in patients attending a fertility clinic in Denmark. We found that 52.5% (n = 145) of women and men reported using vitamins, minerals, herbs and/or alternative treatment. The use frequency was higher among women than among men, which is also reported by other studies [10, 11]. The use increased if the patients had previously received fertility treatment. This trend was also reported in a South Korean study . In concordance with other studies [10, 13], the use prevalence was also higher for participants who had attained education above the primary school level, and the use prevalence increased with increasing level of education.
Complementary and alternative medicine use and infertility
The use prevalence of CAM in patients with infertility has only been sparsely investigated.
This study implied that CAM use is relatively high (52.5%) overall. Other studies estimated that 20-44.7% of patients used CAM for their infertility [14, 15].
Notably, only 53.4% (n = 102) of all women reported consuming folic acid. This prevalence is substantially lower than expected considering that folic acid supplements are recommended both before and during pregnancy as they may prevent birth defects while improving the chance of achieving and maintaining pregnancy . The low folic acid compliance observed was in line with the compliance reported in other studies (42-65.7%) [11, 17].
Pattern in complementary and alternative medicine use in Denmark
In Denmark, the CAM use prevalence in the general population has only been sparsely studied. The CAM use prevalence among pregnant women was found to fall in the 4-69% range [13, 18]. We found herb use prevalence to be 9.2% and 20.7% prior to and during fertility treatment, respectively. However, comparing data requires a more precise definition of the investigated herbs.
Regarding alternative treatment, we found that 27.4% of participants who had received fertility treatment previously used alternative treatment. In contrast, the prevalence in participants who had never received fertility treatment was 16.9%. Other studies have found that the use prevalence of alternative treatment ranged from 20% to 45% in other patient groups [11, 19]. Generally, comparing data from other studies is difficult as study design, CAM definition and local CAM use patterns differ among studies.
Strengths and limitations of the study
The strengths of this study include a rather large study group and a 67.4% response rate, reducing the risk of response bias. Furthermore, the study is likely generalizable as Danish Healthcare provides insemination and up to three IVF stimulations with transfers being readily and equally available to all women in Denmark free of charge. Thus, selection bias is limited as women from all social classes were offered the same treatment options.
One limitation is that most of the participants were Danish-speaking Caucasians. Thus, knowledge about CAM use in non-Danish speaking, non-Caucasian patients is lacking. Furthermore, the risk of recall bias may be a limitation. In the present study, participants had to remember their use of CAM within the past three months or more. Answering the survey online may provide a more precise indication of the real consumption than a stressful situation at the outpatient clinic.
Implication of the findings and further studies
Further research is needed to investigate the extent of CAM use for fertility enhancement. As CAM varies in both frequency and contents between cultures, each fertility clinic should be aware of its local patterns to optimize the fertility treatment and guidance of the patients.
An enhanced focus on information about folic acid supplements to prevent birth defects is urgently needed based on the low use prevalence of folic acid in this study. In general, Danish Healthcare has very limited focus on CAM, and few patients inform their doctors of their CAM use [13, 20].
The high CAM use frequency reported herein underpins the need for further investigation of the efficacy and safety of alternative medicine use during fertility treatment, especially as the quality of the evidence across CAM methods during fertility treatment is poor .
More than half of the Danish women and men initiating and undergoing fertility treatment in this study had been using the investigated CAM within the past three months. Participants who had received fertility treatment previously recorded a significantly higher use of alternative treatment and herbs than participants who had not previously received fertility treatment. Women had a significantly higher use of alternative treatment and herbs than men. However, only about half of the Danish women consumed the recommended folic acid supplementation. This topic urgently needs more attention as folic acid supplementation has been proven to reduce birth defects. Furthermore, the fact that the frequency of CAM use increased during treatment underpins the need for further investigation of the safety of complementary and alternative medicine use during fertility treatment.
Correspondence Anne Dige Soegaard. E-mail: firstname.lastname@example.org
Accepted 10 November 2021
Conflicts of interest Potential conflicts of interest have been declared. Disclosure forms provided by the authors are available with the article at ugeskriftet.dk/dmj
Acknowledgements The authors take this opportunity to express their gratitude to the staff at the Fertility Clinic in Horsens for encouraging their patients to participate, and to the patients for their kind participation.
References can be found with the article at ugeskriftet.dk/dmj
Cite this as Dan Med J 2021;68(12):A05210433
Ernst E, Chrubasik S. Phyto-anti-inflammatories - a systematic review of randomized, placebo-controlled, double-blind trials. Rheum Dis Clin North Am 2000;26:13-27,vii.
Kennedy DA, Lupattelli A, Koren G, Nordeng H. Herbal medicine use in pregnancy: results of a multinational study. BMC Complement Altern Med 2013;13:355.
Sarris J, Panossian A, Schweitzer I et al. Herbal medicine for depression, anxiety and insomina: a review of psychopharmacology and clinical evience. Eur Neuropschopharmacol 2011;21:841-60.
Hall HG, Griffiths DL, McKenna LG. The use of complementary and alternative medicine by pregnant women. A litterature review. Midwifery 2011;27:817-24.
Hwang JH, Kim Y, Ahmed M, et al. Use of complementary and alternative medicine in pregnancy: a cross-sectional survey on Iraqi women. BMC Complement Altern Med 2016;16:191.
Bowen KJ, Harris WS, Kris-Etherton PM. Omega-3 fatty acids and cardiovascular disease: are there benefits? Curr Treat Options Cardiovasc Med 2016;18:69.
Miner Skye A., Robins S, Zhu YJ et al. Evidence for the use of complementary and alternative medicines during fertility treatment: a scoping review. BMC Complement Altern Med 2018;18:158.
Van Gool JD, Hirche H, Lax H, De Schaepdrijver L. Folic acid and primary prevention of neural tube defect: a review. Reprod Toxicol 2018;80:73-84.
Ahmed M, Hwang JH, Choi S et al. Safety classification of herbal medicines used among pregnant women in Asian countries: a systematic review. BMC Complement Altern Med 2017;17:489.
Ekholm O, Christensen AI, Davidsen M, Juel K. Rapport. Alternativ behandling – resultater fra Sundheds- og sygelighedsundersøgelsen 2013. Syddansk Universitet, 2013. https://www.srab.dk/files/Aktuelt/alternativ_behandling._susy_2013_001.pdf
Murto T, Svanber AS, Yngve A et al. Folic acid supplementation and IVF pregnancy outcome in women with unexplained infertility. Reprod Biomed 2014;28:766-72.
Hwang JH, Kim YY, Bin Im H et al. Complementary and alternative medicine use among infertile women attending infertility speciality clinics in South Korea: does perceived severity matter? BMC Complement Altern Med 2019;19:301.
Volqvartz T, Vestergaard AL, Aagaard SK et al. Use of alternative medicine, ginger and licorice among Danish pregnant women - a prospective cohort study. BMC Complement Altern Med 2019;19:5.
Bardaweel SK, Shehadeh M, Suaifan GA et al. Complementary and alternative medicine utilization by a sample of infertile couples in Jordan for infertility treatment: clinics-based survey. BMC Complement Altern Med 2013;13:35.
Coulson C, Jenkins J. Complementary and alternative medicine utilisation in NHS and private clinic settings: a United Kingdom survey of 400 infertility patients. J Exp Clin Assist Reprod 2005;42:5.
Van Gool JD, Hirche H, Lax H et al. Folic acid and primary prevention of neural tube defect: a review. Reprod Toxicol 2018;80:73-84.
Kancherla V, Wagh K, Johnson Q et al. A 2017 global update on folic acid-preventable spina bifida and anencephaly. Birth Defects Res 2018;110:1139-47.
Aagaard SK, Larsen A, Andreasen MF et al. The use of complementary and herbal medicine in the general population and among pregnant women. Ugeskr Læger 2017;179:V08160586.
Lønroth HL, Ekholm O. Alternative therapies in Denmark - use, users and motives for the use. Ugeskr Læger 2006;168:682-6.
Vaabengaard P, Clausen LM. Surgery patients' intake of herbal preparations and dietary supplements. Ugeskr Læger 2003;165:3320-3.