Investigating perceptions and usage of fertility supplements: a mixed methods analysis of a large online forum

Reddit is a worldwide online forum platform which allows its users to create discussion boards called a “subreddit” for any topic of interest. Several subreddits relating to infertility and ART were considered as data sources for this study. One titled “r/IVF” identifies itself as a “supportive and positive community to discuss your IVF journey” with the preface by its creator to “please be sensitive and kind.” This subreddit has high user volume by both women and men, with over 47,000 users as of August 15, 2024. The members who post in this forum consistently self-identify as patients undergoing ART treatments. Despite the title, users were not limited to those undergoing IVF—many discuss oocyte/embryo cryopreservation and intrauterine insemination (IUI). The forum was moderated based on a series of rules outlined in the forum guidelines, which prohibited the sale of medication and discouraged posts by self-identified experts in the field. These rules were beneficial to the study as it prevented posts promoting supplement products and discouraged posts by medical providers, respectively.

A preliminary search for the word “supplement” revealed a high volume of posts which mentioned fertility supplements. The researchers determined that the content of these posts provides a broad picture of patient experiences with fertility supplements during and in preparation for ART treatments. Authors freely express themselves within the forum rules, allowing the subreddit to serve as a window into their perspectives [10]. For these reasons the subreddit r/IVF (https://​www.​reddit.​com/​r/​IVF/​) was ultimately selected as the data source for this study.

The Reddit application programming interface (API), which allows users to sort posts based on whether they contain an input “keyword.” A search within the r/IVF subreddit was conducted three times over the course of two months using the keyword “supplement.” The conjured posts were then sorted by “most recent” to avoid the filtering of posts based on low audience engagement. A search for posts on the r/IVF subreddit was conducted three times over the course of two months, and 449 posts published between April 10, 2024, and June 27, 2024, were found. The posts were extracted and organized using Excel. Comments on the post by other Reddit users were not included in our analysis.

The data collected were from posts published autonomously online by anonymous Reddit users. Obtaining formal consent by Reddit post authors for use by researchers is not possible. Based on the precedent of numerous published studies using Reddit posts for qualitative research with similar methods, this study was not reviewed by an IRB. The post authors’ usernames and any personal identifiers from their posts were not recorded during the study.

A mixed methods, sequential explanatory design was used to collect qualitative data of Reddit posts and then make sense of these findings using quantitative analysis [11]. Qualitative analysis was completed using a combined deductive and inductive approach. Two researchers began by analyzing a small, random subset of posts and identifying areas of interest and emerging themes. Preliminary inclusion and exclusion criteria were to include posts if their use of the word “supplement” was in reference to fertility supplements and to exclude duplicate posts and posts that used the word “supplement” in contexts unrelated to fertility. The preliminary codebook, including one code which established meeting inclusion criteria, included 9 codes.

During analysis, inclusion criteria were revised based on emerging understanding of the dataset to include over-the-counter medications used off-label for fertility purposes, and the exclusion criteria were updated to exclude posts that referred to prescribed IVF protocol medications (i.e., progesterone) or prescription medications (i.e., metformin) as “supplements.”

To establish interrater reliability, both researchers coded the first 50 posts and met to resolve discrepancies. The code was revised, and this process was repeated until the standard for acceptable reliability (> 80%) was met. All remaining posts were coded by researchers individually using an inductive approach, with researchers collaboratively developing further code based on emerging themes. As new code was added, the researchers returned to previously coded posts to complete analysis, with the final codebook containing 12 codes. The final data sets of both researchers were compared at the end of data coding for interrater reliability due to the addition of new codes. The researcher’s codes were found to have “excellent” (> 80%) agreement. All remaining disagreements were discussed and resolved.

Descriptive statistics were used for quantitative assessment of the number of applications of each code to a post via Excel. Named supplement mentions were quantified to identify which supplements were discussed most often. Named supplements in posts containing positive or negative mention of supplements and posts categorized as seeking advice related to supplements were quantified.

The most common class of supplement mentioned was antioxidants. Oxidative stress has been hypothesized as a mechanism of oocyte aging, and antioxidants have been theorized to improve oocyte and sperm quality by scavenging reactive oxygen species (ROS) and preventing gamete damage by oxidative reactions [12, 13]. The most frequently mentioned supplement in this study was CoQ10, an antioxidant which occurs naturally in ovarian follicles [14]. The quantity of CoQ10 in the ovarian follicle diminishes with age and is believed to contribute to eventual depletion of ovarian reserve [14]. Randomized-controlled trials (RCTs) and other studies have been performed to assess the effectiveness of CoQ10 with promising results, such as increased number of retrieved oocytes, higher fertilization rates and more high-quality embryos [15, 16]. Importantly, CoQ10 has shown potential to increase clinical pregnancy rates but has not shown significant increase in live birth rates or decrease in miscarriage rates [17]. Similarly, an RCT of infertile men taking CoQ10 found improved sperm parameters [18]. However, antioxidants have not all been well studied in their ability to improve gamete quality or increase rates of successful ART outcomes. Acai berry has been recommended based on a study demonstrating an effect on oocyte aging in mice and an ongoing RCT in human subjects [19]. However, there are no complete human studies in our literature search demonstrating acai’s effect on ART treatment outcomes.

Other supplements theoretically improved endometrial thickness and receptivity through vasodilatory effects, increasing blood flow to the uterus [20]. The most common “supplements” with this desired effect were low-dose aspirin (LDA), followed by L-arginine [20, 21]. Beet root juice and other natural juices with vasodilatory effects have been studied as a supplement to IVF with positive results [22]. Brazil nuts are supplemented for their selenium content, which has a mild anticoagulative effect and may improve endometrial thickness [23, 24]. While these effects may be beneficial, combining vasoactive supplements may incur bleeding risk or otherwise be harmful [25, 26].

Anti-inflammatory medications such as prednisone are thought to decrease the immune response after embryo transfer or oocyte retrieval and have been recommended to improve endometrial receptivity [27]. Antihistamines, such as Benadryl, are taken off-label for this purpose by some patients [28]. Their use is controversial, as some studies have reflected that they may inhibit implantation and may also increase risk of subchorionic hematomas in the first trimester [28‐30].

Researchers believe the vaginal microbiome may affect overall reproductive health [31]. Probiotics are being studied to target dysbiosis of the vaginal or endometrial flora, which may be detrimental to implantation in infertility patients; however, more data is needed to determine the impact of probiotics on ART outcomes [32]. Our study recorded 12 mentions of probiotics (Table 2), with 4 mentions associated with posts seeking advice (Table 6), suggesting that this is another area of study that would benefit patients.

Several underlying causes of infertility have been targeted by supplements. Myo-inositol has been studied as a supplement for patients with PCOS due to its insulin sensitizing effects [33]. DHEA, an androgen precursor necessary for ovarian stimulation and response, decreases with age and may be supplemented in patients with diminished ovarian reserve [34]. An association between vitamin D deficiency and infertility has been observed, particularly in patients with PCOS [35]. Vitamin D is required for calcium absorption, which is necessary for oocyte maturation [36]. The supplementation of vitamin D in deficient patients is often recommended by providers and the posts analyzed in this study frequently noted a perceived positive effect on labs and outcomes.

More than half of the subjects in our study reported taking multiple supplements at once. There may be harmful interactions when combining supplements or taking them with medications. For example, vitamin E may increase the potency of LDA, which is sometimes taken to improve endometrial blood flow and support implantation [25, 37]. Many patients may be unaware of these risks, and the safety of the use of multiple supplements may be difficult to ascertain. The risk of adverse events from supplements can be difficult to trace given the retroactive regulation of these products [38]. Even food-based products that are generally considered safe pose risk for allergic reactions as described by one subject in this study allergic to acai (Table 5).

The proportion of post authors seeking advice on the IVF subreddit (16%) as well as the number of post authors interested in beginning fertility supplements (21.9%) highlights a need for guidance on their use. Many subjects had legitimate questions, and some described concern for inadvertent misuse of the supplements (Table 6). Several authors expressed dissatisfaction with the degree of knowledge and interest shown by their provider on the topic. Lack of proactivity on the part of providers to address supplement use may be damaging to the patient-provider relationship and lead patients to seek anecdotal advice online.

Patients were aware of the conflicting opinions among providers, and some appeared to be negatively impacted by the uncertainty (Table 6). The lack of literature and society guidelines available on many of these supplements may contribute to provider reluctance in providing recommendations on supplement use. Many supplements have limited studies investigating their efficacy, which leads some providers to recommend them while others are hesitant to do so without more robust studies.

A self-help book series It Starts With The Egg was written to provide patient-friendly information on supplements [39]. This book series was frequently cited in posts in the IVF subreddit, and many patients based their supplement use on the book’s supplement lists and contents. This shows that the development of standardized protocols and indications for supplementation are desired by patients. Discussing evidence-based literature and recommendations with patients may allow for joint decision-making while preserving trust in their providers.

Due to the anonymity of Reddit users, demographic information could not be collected for the study. Therefore, the diversity of the population observed cannot be determined. It is possible the post authors represent a subset of IVF users that differ from the general population. Patients may be more inclined to post on the IVF subreddit if they have had lack of success in their fertility journey, are in an emotionally heightened state, or have a poor patient-provider relationship, all of which are a potential source of bias. Additionally, we could not verify whether a post’s author was a real patient, a bot, or a marketing employee posing as an ART patient.

One of the benefits of Reddit for social media analysis over other platforms is that it does not exclusively use an interest-based algorithm to sort posts like other social media websites. Despite this, Reddit policies may screen or hide posts based on author usership, relevance, popularity, and accordance with the subreddit guidelines, which could potentially affect the data in our study.

We examined post content with the goal to observe patient experiences with fertility supplements and identify areas where research is needed; however, we could not ask guided questions and therefore may not capture a complete picture of our subjects’ experiences. A survey or focus group is a future direction for validating our conclusions. Furthermore, despite excellent interrater agreement, the rater’s interpretations of post tone or attitude may not always reflect that intended by the author.

Finally, the claims about perceived effects of supplements on ART success by subjects are presumably anecdotal. The data in this study cannot be used to draw conclusions on the effectiveness or safety of named fertility supplements. Future studies should aim to objectively characterize the benefits and risks of supplement use by ART patients.