Examining reasons that patients discard cryopreserved oocytes

Abstract

Purpose

Assess the rate, rationale, and characteristics of patients who cryopreserved and subsequently discarded their oocytes, and compare their characteristics to patients with continued cryopreservation of oocytes.

Methods

All patients who disposed of cryopreserved oocytes between 2009 and 2022 reported their reason for discarding their oocytes. This was a retrospective cohort study.

Results

Of 5,010 patients who underwent oocyte cryopreservation (OC) cycles, 201 (4%) patients elected to discard their oocytes and 751 (15%) thawed oocytes for clinical use. The average ages of OC and disposal were 35 and 39 years old, respectively. Of the 201 patients who discarded their oocytes, 71 patients (35%) requested disposal after having a child. Twenty-six (13%) discarded oocytes because of worsening cancer and three (1.4%) discarded because of death. 16 (8%) discarded oocytes due to cost of cryopreservation and eight (4%) due to low oocyte yield. Ten (5%) patients underwent new IVF cycles and discarded previously stored oocytes. Sixty-seven patients (33%) discarded oocytes for unspecified reasons. When comparing patients who discarded oocytes with those who did not, the former had lower AMH (2.7 vs 3.5 ng/ml, p < 0.001) but otherwise comparable age and number of cryopreserved oocytes. The mean age for those with continued cryopreservation was 35.4 years at time of OC and 40 years at time of data collection in June 2023.

Conclusion

Childbirth was the most common reason to dispose of oocytes followed by unspecified reasons. Larger studies of oocyte disposal may better define clinical characteristics of patients most likely to use, maintain or discard their oocytes.

Introduction

Oocyte cryopreservation (OC) was originally intended to preserve future fertility in cancer patients who required gonadotoxic cancer treatments [1]. Later, OC was extended to patients with non-oncologic conditions treated with medications or surgeries that threaten ovarian reserve, including ovarian endometriosis [1]. More recently, OC has been pursued by women wishing to delay childbearing, with a view to protecting against age-related loss of fertility potential [1, 2]. This “elective” OC became prevalent in the early 2000s [1]. The clinical success of live birth rates from cryopreserved oocytes was unknown when oocyte vitrification was initially developed and implemented [1, 2]. Subsequently, many studies have confirmed that clinical pregnancy rates and live birth rates of cryopreserved oocytes are comparable to age-matched fresh oocytes cycles, though there can be 10–20% loss of oocytes when thawed [3, 4].

Elective OC is cost effective, particularly when done prior to age 38 [5, 6]. The number of cryopreserved oocytes increases the likelihood of a live birth, with the recommendation of 15–20 mature (metaphase II, M2) oocytes for women < 38 years old and 25–30 M2s if 38–40 years old [1, 4]. Many obstetrician/gynecologists have mixed feelings regarding elective OC. A majority cite concerns regarding the treatment process and efficacy and chose not to routinely discuss the process with patients [7]. Most providers discuss OC with cancer patients as well as with patients who have other medical indications [7]. Given the proven negative effects of age on reproductive potential, the ethical principle of autonomy, and the safety and efficacy of the fertility preservation process, we believe that women deferring reproduction should be informed of and have access to OC.

We continue to learn more about the women who pursue OC and their experiences with treatment. Recent studies have indicated that the most common reason for elective OC is the lack of a partner; 15–25% subsequently use their cryopreserved oocytes, and few regret their decision to pursue the treatment [2, 8]. In the USA, cryopreserved oocytes can be stored indefinitely, used clinically or for research, or discarded [9, 10]. Little is known about the fraction of patients who discard cryopreserved oocytes and what factors underly this decision.

A recent systematic review of 22 studies, both international and in the USA, included data on the intentions of patients with unused cryopreserved oocytes [10]. Eight studies involved elective OC cycles of which 53% of patients intended to donate surplus oocytes to research, 31% were unsure, 26% would donate to family members/friends/patients, and 12% would discard their oocytes. Regarding oocyte donation, some were uncomfortable with the prospect of having an unknown biological child or a biological child raised by a relative or friend [10]. The researchers observed that intentions towards cryopreserved oocytes changed over time and that there seemed to be inadequate communication and psychosocial support for patients as they navigated decisions about fertility [10]. This was further validated by a study which determined that patient autonomy and support from others improved the decision-making process, allowed patients to practice shared-decision making, and resulted in patients feeling empowered as they consider fertility preservation [11].

Our study sought to determine the most common reasons for which patients disposed of cryopreserved oocytes as well as basic characteristics of these patients. Patients were queried at the time of their request for oocytes disposal. We then compared these patients against those with continued OC to see whether there was any difference in basic clinical characteristics. Herein, we report the reasons for oocyte disposal as well as descriptive factors, including length of time cryopreserved, age, and number of oocytes discarded from this cohort of patients, and we compare this group with those who continue to maintain their cryopreserved oocytes.

Materials and methods

Study design

Retrospective cohort study of all women who discarded cryopreserved oocytes compared to those with continued OC after having undergone elective or medically-indicated OC from autologous cycles from 2009 to 2022 at a large, multisite, private practice with locations in Washington D.C., Maryland, Virginia, and Pennsylvania. This retrospective review was IRB approved.

Patients

All patients who had undergone cryopreservation and then decided to discard their oocytes or continue OC were included for analysis. These were all autologous cycles with standard IVF protocols for oocyte retrieval and vitrification performed as previously described [12]. No slow-freeze cycles were included. Patient who thawed some of their oocytes but not all were excluded from the study.

Patients disposing of their cryopreserved oocytes were required to provide the reason for disposal as a part of quality analysis for the IVF laboratory. Reported reasons for disposal followed a single-choice option that included: a) worsening cancer, b) cost, c) death of the patient, d) low oocyte yield, e) achieved family building goals by utilizing some (but not all) of the OC or newly retrieved oocytes in autologous cycles, or independent of fertility treatment and, f) other/personal. If the patient did not include the reason for discard, they were placed in the “other” category. Patients were only able to select one option.

Outcomes and definitions

The primary outcome measure was the patient-reported reason for disposing of cryopreserved oocytes. Secondary outcomes were the age at time of cryopreservation, age at time of disposal, number of oocytes, rate of oocyte discard, and rate of oocyte use. We also compared age at cryopreservation, number of oocytes, BMI, and AMH from those who opted to discard against those who continued to store their cryopreserved oocytes at time of data collection in June 2023.

Statistical analysis

Descriptive statistics were used to demonstrate the mean and standard deviation for continuous variables. Categorical variables were expressed as case number and percentages. Student’s t-test was used to analyze difference between means, with p < 0.05 considered statistically significant.

Results

More than five thousand (5,010) patients underwent autologous OC (2009–2022) from which 201 patients (4%) subsequently requested oocyte disposal; these patients are the focus of our analysis (Fig. 1). No patient donated their oocytes for research purposes or for reproductive use. Seven hundred fifty-one (15%) of patients thawed their oocytes for clinical use in order to conceive. A total of 4,058 patients opted to continue cryopreservation. Of the 201 patients who elected to discard, 26 had preserved their oocytes in the setting of a cancer diagnosis (i.e., onco-fertility preservation). The average age at time of oocyte retrieval was 34.8 years old. An average of 11.9 mature oocytes were obtained. The average age at time of disposal was 39.4 years old. Oocytes were stored for a mean of 4.6 years prior to disposal (Table 1).

Fig. 1.

Breakdown of patients who discarded oocytes because of ongoing pregnancy or live birth

Table 1.

Reasons for oocyte disposal and basic characteristics

	All Reasons	Cancer	Cost of cryopreservation	Death	Low oocyte yield	Made new embryos	Pregnant or Live Birth	Other
	n = 201	n = 26	n = 16	n = 3	n = 8	n = 10	n = 71	n = 67
Age at cryopreservation, years	34.8 ± 5	30.2 ± 7	35.8 ± 5	29.0 ± 7	33.5 ± 14	37.4 ± 5	35.2 ± 5	36.1 ± 4
Age at disposal, years	39.4 ± 7	35.1 ± 7	41.2 ± 7	32.3 ± 6	36.6 ± 15	39.5 ± 4	39.7 ± 5	41.0 ± 5
Length of time cryopreserved, years	4.6 ± 3	5.0 ± 3	5.5 ± 3	3.4 ± 1	2.8 ± 3	2.1 ± 2	4.5 ± 3	5.0 ± 3
Total number of oocytes frozen	11.9 ± 7	15.2 ± 9	11.3 ± 5	12.3 ± 8	3.4 ± 4	3.9 ± 3	12.0 ± 7	12.7 ± 7

Mean ± Standard Deviation

When comparing those who discarded embryos with those who continued OC, there was no difference in age at cryopreservation, number of oocytes cryopreserved, or BMI but a lower AMH in those with continued OC (3.5 vs 2.7 ng/ml, p < 0.001) (Table 2). In the continued OC population, their mean age at cryopreservation was 35.4 years. The mean age at time of data collection is 40.4 years old and they have stored for an average of 4.5 years.

Table 2.

Basic characteristics of those discarding oocytes vs those maintaining their cryopreserved oocytes

	Oocyte Discard	Continued Cryopreservation	P value
	n = 201	n = 4058
Age at cryopreservation, years	35.8 ± 6	35.4 ± 13	0.5
Total number of oocytes frozen, years	11.9 ± 7	11.9 ± 8	1
BMI	25.2 ± 5	24.9 ± 5	0.4
AMH	3.5 ± 5	2.7 ± 3	< 0.001

Mean ± Standard Deviation

In our cohort of patients who discarded oocytes, 71 (35%) patients reported having at least one child as their reason for oocyte disposal (Fig. 1). From this subset, twenty-one patients reported conceiving naturally and the remainder (50 patients) reported using fertility treatments to conceive. Of the 50 patients using fertility treatments to conceive, 43 patients thawed some, but not all, of their cryopreserved oocytes in order to conceive by IVF. Two patients did not get pregnant using the cryopreserved oocytes and achieved pregnancy through donor oocytes, opting to discard their cryopreserved oocytes. The age at cryopreservation and age at disposal were similar between those who reported conceiving naturally versus those using stored oocytes who achieved a successful pregnancy with the stored oocyte (34.0 and 38.9 years old, and 35.67 and 40.0 years old, respectively) (Fig. 2).

Fig. 2.

Reasons for oocyte disposal

Overall, 67 (33%) patients reported discarding their oocytes for unspecified reasons (personal/other), 26 (13%) discarded their oocytes due to cancer progression, three (1.4%) had oocytes discarded due to death of the patient (these were all onco-fertility patients). Sixteen (8%) patients discarded oocytes due to the ongoing cost of cryopreservation and eight (4%) disposed of oocytes due to low oocyte yield from their stimulated cycle(s). Ten (5%) patients underwent new IVF cycles and reported discarding their cryopreserved oocytes for that reason.

The average age at OC, age at disposal, length of time cryopreserved, and total number of oocytes cryopreserved varied by the reason for oocyte disposal (Table 1). Cancer patients who subsequently had a poor response to treatment, or died, were the youngest at the time of OC. Patients who discarded oocytes after pursuing new IVF treatments were the oldest at the time of discard (39.5 years old). Patients discarding oocytes due to OC fees had the longest time of OC (mean of 5.5 years). Onco-fertility patients cryopreserved the highest number of oocytes (15.2 M2s). Patients who proceeded with additional ART cycles to produce new embryos had the shortest time of OC (mean of 2.0 years).

Discussion

According to recent data, elective OC has become an increasingly frequent practice, with SART reporting over 13,000 oocyte cycles in 2018 compared to just 475 in 2009 [13]. Motivations for electively cryopreserving oocytes center on two principal factors: the desire delay childbearing and the lack of a reproductive partner [8, 14–17]. In addition, OC is routinely offered to cancer patients and to patients with conditions for which treatment can similarly impair oocyte supply [1–4]. The overall process of OC is both emotionally and physically demanding as well as costly. Estimated costs per cycle average $10,000 dollars plus the costs of stimulation medications and the recurring costs of OC [5, 6, 14, 15]. Some patients require more than one stimulation cycle to obtain the desired number of oocytes for cryopreservation [4].

To date, most cryopreserved oocytes are neither utilized clinically nor discarded [1, 2, 13–16]. Our data support an extremely low disposal rate of 4%, and a large number of patients opting for continued cryopreservation (Table 2). As observed for all autologous fertility treatments, clinical outcomes with cryopreserved oocytes decline with increasing age at the time of retrieval [14]. Research on why patients discard cryopreserved oocytes is limited even though most ART practices require patients to give a reason for disposal [10, 13]. To date, little has been reported regarding the average time of cryopreservation or other basic characteristics of OC and disposal in elective or medically-indicated OC cycles. Although the number of OC has increased significantly over the past decade, longitudinal data on what women choose to do after cryopreservation, and what motivates these decisions, are lacking.

Our study provides insight into the reasons why women dispose of their cryopreserved oocytes. A sizable percentage of patients discarded oocytes after having at least one child. Some patients were able to achieve their family building goals and were fortunate enough to have surplus oocytes. Most patients who conceived reported spontaneous conceptions prior to disposing of their stored oocytes, though others required fertility treatments. Some patients underwent contemporaneous IVF rather than utilize cryopreserved oocytes; our retrospective analysis is unable to determine the rationale for this decision. We can speculate that these patients viewed their cryopreserved oocytes as “backup plans” should de novo IVF treatments fail, but this remains speculative.

Additional limitations of this study include that the data were self-reported and that many respondents (33%) discarded oocytes for unspecified/personal reasons. We cannot comment on why these patients discarded their cryopreserved oocytes and further research is warranted to understand their motivations. It seems likely that our list of reasons for discarding oocytes did not apply to all patients who discarded oocytes and that important additions to future questionnaires might include additional choices (i.e., no longer desires offspring), might allow for multiple selections, and might provide space to “write-in” patient-derived responses.

We also cannot comment on the nearly 80% of patients who have neither thawed nor disposed of their oocytes. While those with continued OC had lower mean AMH values compared with those that discarded oocytes, it remains unclear whether this measure of ovarian reserve played a role in the decision to maintain cryopreserved oocytes. It will be important to better understand what circumstances and motivations lead to the long-term cryopreservation of oocytes for the majority. Whether these oocytes will someday be used clinically, donated, discarded, or abandoned, remains to be seen. Many fertility centers, for medical and ethical reasons, have age limits above which embryo transfers are not offered; such limitations could come as a shock to patients not warned of the consequences of delaying fertility. Further, there are medicolegal concerns regarding how centers should manage abandoned oocytes.

Only 4% of cryopreserved oocytes were discarded over the 13-year period that we studied. Our work offers some understanding for why women discard their cryopreserved oocytes. Interesting, as well, is why a majority of women in our cohort neither utilized nor discarded their cryopreserved oocytes. Elective OC generally begins with the decision to defer having children. Common reasons for this include lack of resources or desire to reproduce—sometimes coupled with a desire to avoid single-parenting and an understanding that fertility potential declines with age. Many place hope in their future, whether this be expectations regarding future employment, anticipated financial resources, or partnering prior to co-parenting. Given the thought, effort, and resources that go into cryopreserving oocytes it is perhaps not surprising that discarding oocytes is neither common nor sudden [10] . Further outcomes data regarding cryopreserved oocytes may identify those that most benefit from this important medical advancement. A better understanding with respect to those choosing to discard oocytes might identify women for whom OC is unnecessary or ill-advised.

Conclusion

We highlight reasons women discard cryopreserved oocytes. Pregnancy accounts for over a third of patients who discard their oocytes and is more likely to occur in younger women. Another third of patients discard stored oocytes for unspecified reasons while smaller proportions discard for reasons of cost, cancer, death, or low yield of oocytes. Future studies are needed to better understand the factors influencing patient utilization and disposal of oocytes. Such work will help guide patient counseling and clinical decision making with respect to elective and non-elective fertility preservation through OC.

Data availability

Data regarding study subjects has not been previously published. Primary data will be made available to editors, reviewers, or researchers upon request.

Declarations

Ethical approval

IRB approved—The Advarra Institutional Review Board approved the retrospective review and analysis of the data collected during routine clinical care; Shady Grove Fertility Reproductive Science Center—R2009.1, Retrospective Analysis of Factors Associated with Outcomes of Infertility Treatment (Pro00027148).

Informed consent

Not required.

Conflict of interest

The authors declare no competing interests.