Disposition preferences in oocyte preservation patients

Abstract

Purpose

To characterize the frozen oocyte disposition preferences of patients undergoing medical and planned fertility preservation.

Methods

All oocyte cryopreservation (OC) patients were identified between 2015 and 2018. Demographic information and fertility preservation (FP) indication (medical or planned) were identified for each patient. Oocyte disposition options included disposal, donation to research, or donation to a specified third party, which was decided at the time of initial consent and made available in the electronic medical record. The primary outcome was the disposition selection. Secondary outcomes included differences in demographic variables and disposition selections between medical and planned FP patients using chi-squared analysis.

Results

A total of 336 OC patients with a documented oocyte disposition preference were identified in the study timeframe. Patients were on average 34.5 years old (SD = 5.1) and were predominantly White (70.2%), nulliparous (83.0%), with a BMI of 24.7 (SD = 5.4). A total of 101 patients underwent OC for medical FP and 235 for planned FP. In both groups, the most commonly selected disposition option was donation to research (50% planned, 52% medical), followed by donation to a specified third party (30% planned, 30% medical), and finally disposal of oocytes (20% planned, 18% medical). There were no significant differences in disposition selection between each group. When comparing patient variables between groups, medical FP patients were more likely to be under the age of 35 and were less likely to be nulliparous (p < .001).

Conclusion

This study shows that oocyte disposition choices are similar in patients undergoing OC for medical and planned indications. As donation to research was the most commonly selected option in both groups, it is time to start thinking of streamlining ways to utilize this potential research material in the future.

Introduction

Oocyte cryopreservation (OC) for fertility preservation (FP) has become increasingly prevalent for both planned (“elective”) and medical indications [1, 2]. The annual number of OC cycles has increased from 6090 in 2014 to 16,194 in 2019 [3, 4]. Coinciding with the rise in average age of first-time mothers in the USA and increased public support for planned OC [5–7], women have increasingly opted to undergo FP in an attempt to minimize biologic pressures on family building despite FP not guaranteeing future fertility [8, 9]. Women in time-intensive professions have increasingly chosen FP to defer childbearing [10, 11], and pre-professionals have viewed company provided financial coverage for OC as a benefit to workers rather than as coercive [12]. Similarly, patients diagnosed with a condition requiring gonadotoxic treatments may elect FP prior to treatment to maximize potential for future genetic family building [2]. While the increase in FP has improved quality of life measures for patients who may have otherwise been infertile, it has been observed that this trend may represent a major shift in goals for undergoing procedures for reproduction, from that of having a child at present to more of a speculative fertility with the goal being the ability to have children in the future [9].

Although there is not much data on rates of frozen gamete use after FP, there are indications that many FP patients do not return to use their gametes [13–16]. Many women may undergo FP but ultimately conceive naturally, change their mind on family building later in life, not utilize their frozen oocytes due to the lack of a partner, or fear obstetric complications due to advanced maternal age [17, 18].

Prior to undergoing a controlled ovarian hyperstimulation cycle at our center, patients are asked to elect an oocyte disposition preference in the event of death or incapacitation while the oocytes are in storage: discard unused gametes, donate unused gametes to a person of the patient’s choosing, or donate unused gametes to research. Although studies on oocyte disposition are limited, previous studies have documented a trend in patients choosing to discard frozen embryos rather than donate to research [19–22]. Many patients also opt to keep their embryos in storage indefinitely and many embryos are considered abandoned with no disposition decision resulting in a storage burden on clinics and cryopreservation companies [23]. Difficulty with decision-making related to embryo disposition is often associated with a patient’s ethical or emotional concerns related to the destruction or donation of the genetic material [24]. However, since an oocyte represents an unfertilized gamete, and thus might be associated with different ethical/moral belief systems than those associated with embryos, it is important to study disposition in this regard as well.

Despite the recent viability of OC due to improved vitrification technique and increasing number of FP cases, there is still a gap in knowledge regarding disposition preferences for frozen oocytes and whether those preferences are associated with planned OC or medical indications for FP.

The minimal research on oocyte disposition intent shows conflicting findings with the studies being marked by small sample sizes, retrospective survey, and without direct comparison of intent in planned versus medical OC [25]. With the current trend of many FP patients not returning to use their frozen gametes, disposition preferences for frozen gametes have become a vital topic of inquiry due to the potential storage burden of unused oocytes, the untapped potential of oocytes donated for research, and the potential emotional concerns of patients engaging in disposition decisions. In this study, we aim to characterize the frozen oocyte disposition preferences of patients undergoing planned and medical FP. Similar to what prior work on oocyte disposition intentions has shown, we hypothesize that the majority of patients in both FP groups will elect to donate frozen oocytes for research.

Materials and methods

Study design

Institutional Review Board (IRB) approval was obtained for this retrospective clinical comparative study. Data was collected on all patients who had consulted for FP from 2015 to 2018 based on electronic medical record documentation.

Measures

Demographic and stimulation data were collected for each patient. Medical diagnosis was collected for each medical FP patient. Medical and planned FP patients were distinguished based on documentation in their initial consult note in the electronic medical record. Disposition selection took place at the time of the initial consent discussion with a physician and was documented in the medical record. Patients were asked to select a disposition option in response to the question “In the event of death or incapacity while my oocytes are in storage, I instruct authorized personnel dispose of my oocytes as follows,” and were given the following options to choose from: discard all oocytes, donate all oocytes for an IRB approved research project, or donation to a specified third party. The disposition preference selected by patients is not legally binding. The primary study outcome was the frequency of selection of each disposition option. Secondary outcomes included differences in demographic characteristics and disposition selections between medical and planned FP patient groups.

Data analysis

The demographic characteristics and disposition selections for medical and planned FP patients were compared using chi-square analysis with pairwise Z-tests. All p values were two-sided, and a p value of < 0.05 was considered statistically significant. Statistical analyses were performed with SPSS IBM Statistics 26.0 for Windows (SPSS, Chicago, IL).

Results

A total of 349 patients undergoing oocyte vitrification cycles were identified from 2015 to 2018 in the analysis. Thirteen cycles were noted to have no documented disposition preference and were excluded from the analysis. A total of 101 patients were identified as medical FP and 235 as planned FP. Reasons for medical FP included a diagnosis of cancer, hemoglobinopathy (sickle cell anemia and beta thalassemia), scleroderma, gender dysphoria, Turner’s syndrome, and multiple sclerosis.

In both the planned and medical FP groups, the most commonly selected disposition option was donation to research (50% planned, 52% medical), followed by donation to a specified third party (30% planned, 30% medical), and finally disposal of oocytes (20% planned, 18% medical) (Fig. 1). There was no significant difference between the two groups in terms of disposition preference. Medical FP patients were more likely to be under the age of 35 and were less likely to be nulliparous, but all other demographic parameters were similar between the groups (Table 1). Interestingly, we found that women older than 35 years were more like to elect to discard oocytes than women who were under 35 years old (χ² [n = 336] = 8.59; df = 2, p < 0.05). Parity was not associated with disposition decision.

Fig. 1.

Disposition preferences of planned and medical fertility preservation patients

Table 1.

Demographic characteristics of the cohort

	Total (n = 336)	Planned FP (n = 235)	Medical FP (n = 101)	p
Mean age (years)	34.5 ± 5.1	36.3 ± 3.0	30.4 ± 6.5	.435
Age > 35 years (%)	56.8	69.4	27.7	< .001*
Mean BMI	24.7 ± 5.4	24.2 ± 4.9	26.0 ± 6.1	.622
Race/ethnicity (%)				.170
Asian   Black/African   Caucasian   Hispanic/Latino   More than one race   Not reported	14.9 7.1 70.2 5.1 2.4 0.3	15.3 5.5 71.9 4.3 3.0 0	13.9 10.9 66.3 6.9 1.0 1.0
Gravidity (%)				.348
0   1   2   3	83.0 13.1 3.6 0.3	84.7 11.1 3.8 0.4	79.2 17.8 3.0 0
Parity (%)				< .001*
0   1   2	95.8 3.0 1.2	98.7 0.9 0.4	89.1 7.9 3.0

FP, fertility preservation; BMI, body mass index; *p<0.05

Discussion

In the decade since oocyte vitrification has been deemed “non-experimental,” we have seen the utilization of this practice increase exponentially, and with it an increased demand for space and resources to ensure continued safe storage. While OC cycles have been on the rise, to date, we have seen few of these women return to utilize these frozen oocytes, with some studies estimating as low as a 7–38% utilization rate after at least 10 years [26, 27]. This increased demand for oocyte vitrification and storage paired with a low rate of utilization is creating an excess of frozen gametes, but there is a significant gap in knowledge on the intended fate of any future unused oocytes. As the early adopters of OC approach a decade of gamete storage, we anticipate a transition from continued storage to disposition of oocytes in the coming years, making this an important matter to address. Identifying and understanding these preferences can guide future plans for storage and resource utilization, as well as assist with counseling the growing numbers of OC patients on oocyte disposition options and trends.

This study is the first to primarily assess the disposition preferences for unused oocytes in both medical and planned FP circumstances. In this cohort of 336 oocyte vitrification cycles, donation to research was the most favored disposition for frozen oocytes in both the planned (50%) and medical (52%) FP groups. This is consistent with the findings from a recent systematic review that addressed oocyte disposition intentions from 2005 to 2018 among three groups of women: those with surplus oocytes in storage, with intentions to undergo OC, and those of reproductive age [25]. Data on those who had already undergone OC came from eight studies with overall results revealing that over half elected to donate to research, approximately one-third desired either donation to others or were unsure, and only 12% chose disposal. The current study improves upon this prior study by utilizing a large sample with a study design which avoids risk of recall bias and includes a direct comparison of disposition intent in planned and medical FP patients.

Although embryos have generally been less favored for donation, to research or to other individuals, the primary intent to donate oocytes to research in our study may be due to the decreased complex ethical, moral, and legal considerations and challenges associated with oocytes as compared with embryos [19–22, 28, 29]. Historically, obtaining human oocytes for research purposes has been burdensome. Prior to 2007, oocytes utilized in research were largely obtained from oocytes collected for the purposes of in vitro fertilization (IVF), but were deemed “unsuitable” (example: immature, unable to fertilize). In 2007, Human Fertilization and Embryology Authority (HFEA) issued new legislation that allowed women to undergo controlled ovarian hyperstimulation and oocyte retrieval to donate their oocytes for the purposes of research alone in the UK [30]. While this allowed researchers access to good quality oocytes, it proved difficult to recruit for and sparked ethical debate over the risk/benefit ratio. With the acceptance and widespread adoption of oocyte cryopreservation, low oocyte utilization rates and our finding that a majority of patients elect disposition to research in the event of their death or incapacitation, if patients also choose to donate oocytes to research in the event that they simply do not plan to use them, we find ourselves on the precipice of a large influx of good quality oocytes allocated for research purposes. It is crucial for us to anticipate this possible influx of new research materials and to be able develop a streamlined process for oocyte disposition to appropriate IRB approved projects within and across institutions.

An additional finding was that women over 35 years were more likely to select oocyte disposal compared to younger women, and more women in this age group underwent planned OC. While we do not have information on why patients chose a particular disposition option, this finding suggests that different age groups may have distinct motivators and perceptions about their oocytes. Given that women undergoing planned OC likely do not have children and often engage in OC as they do not have a partner with whom to conceive [31], it may be that older women in the planned OC group elect to discard oocytes as they see the primary purpose of their oocytes as a means to help them to have a child; and if they cannot use them because of death or incapacitation, then the imagined purpose for the oocytes is lost. Additionally, research has found that frozen oocytes are often viewed as “cells” (compared to embryos seen as “children” or “potential children”) suggesting that there may be less attachment to oocytes [32–34], and perhaps as women get older, they are more likely to develop this view of oocytes. It may also be that both medical and planned OC patients hold more liberal views about reproduction as they are engaging in treatment that is not consistent with puritan norms for procreation within the context of intercourse within a heterosexual cisgender marriage. With the rising popularity and knowledge of OC, more information on contemporary attitudes towards oocytes across different age groups is needed.

It is important to consider that these initial oocyte disposition selections are not legally binding and thus may change. Prior research has shown that embryo disposition decisions change over time [35], with a shifting of preferences towards embryo disposal after successful IVF treatment or spontaneous conception leading to completion of families or as a result of limitations such as cost or age [22, 36]. If a similar trend is seen with oocytes, this again may suggest that disposition decisions once family building is complete or in the event that the woman is alive but unable to use her oocytes are heavily influenced by a belief that gametes serve a primarily self-focused reproductive purpose. Thaw and discard may also be the most parsimonious option as it requires the least amount of time and other resources whereas donation to research or another person likely requires many steps and assumes suitable research options are available. Given the known shifts in embryo disposition trends towards disposal, it is possible that oocyte disposition preferences will also be subject to similar changing attitudes and influencing factors over time. It is important to note however that compared to research examining embryo disposition intentions, patients in the current study were more likely to elect to donate to another person and somewhat less likely to report intention to donate to research or to thaw and discard. Given the recent trends for embryo disposition towards disposal and away from donation to another person particularly after the birth of a child [36], we hypothesize that similar future trends will be seen for FP patients who later have a child.

The strengths of our study include the large sample size of both planned and medical FP patients. Disposition preferences were obtained at the time of initial OC consent for all patients, allowing for standardization of questions and response options as well as a high response rate. A limitation of the study includes the inclusion of participants from only a single center and that final disposition decisions in the event that patients no longer intend to utilize remaining oocytes are unknown. Although final disposition decisions are unknown, no prior studies have identified similar disposition intentions across medical and planned FP patients suggesting similar beliefs and/or attachment to oocytes among a large group of women seeking treatment for different reasons. This suggests that similar counseling strategies for oocyte disposition may be appropriate for these groups. Additionally, our study highlights the differences between FP patients’ disposition intentions and embryo disposition decisions. Thus, studies of oocyte disposition intentions are also important in order to generate future testable hypotheses about final disposition decisions. Studies on intention provide an important early glimpse into an uncertain future. Few women who have frozen their eggs have made a final disposition decision thus limiting our ability to compare intent with final decision-making, and few studies on intention in FP patients have been published, making this type of research especially important.

Oocyte disposition preference is a new area of research and continued work on this topic is needed. As disposition of oocytes is anticipated to become more relevant and occur in the coming years, future research on actual disposition outcomes and if they differ from initial preferences can offer additional insight. For patients with oocytes that remain in storage, it may be valuable to follow-up and reassess disposition preferences at a later timepoint to examine whether these intentions change over time.

In conclusion, our study provides new insight into oocyte disposition election trends in medical and planned FP patients. Given low oocyte utilization rates and preferential desire for unused oocytes to be used for research, it may be time for the scientific community to begin thinking of streamlining ways for these oocytes to be used in research and make use of this resource that has very rarely been available in the past. We should also start planning for the implementation of protocols to effectively discard undesired oocytes to allow for efficient storage of new oocytes as FP rates continue to increase.

Declarations

Ethics approval

Institutional Review Board (IRB) approval was obtained.

Consent to participate

Waiver of informed consent was approved by IRB given retrospective nature of study.

Conflict of interest

The authors declare no competing interests.