Ovarian stimulation is a safe and effective fertility preservation option in the adolescent and young adult population

Abstract

Purpose

The aim of this study is to describe the multidisciplinary approach and controlled ovarian hyperstimulation (COH) outcomes in adolescent and young adult (AYA) patients (ages 13–21) who underwent oocyte cryopreservation for fertility preservation (FP).

Methods

Multi-site retrospective cohort was performed from 2007 to 2018 at Northwestern University and Michigan University. Data were analyzed by chi-square test, t-test, and logistic regression.

Results

Forty-one patients began COH of which 38 patients successfully underwent oocyte retrieval, with mature oocytes obtained and cryopreserved without any adverse outcomes. To treat this group of patients, we use a multidisciplinary approach with a patient navigator. When dividing patients by ages 13–17 vs. 18–21, the median doses of FSH used were 2325 and 2038 IU, the median number of mature oocytes retrieved were 10 and 10, and median number frozen oocytes were 11 and 13, respectively. Median days of stimulation were 10 for both groups. There was no statistical difference in BMI, AMH, peak E₂, FSH dosage, days stimulated, total oocytes retrieved, mature oocytes retrieved, and oocytes frozen between the two groups. Three patients were canceled for poor response.

Conclusion

COH with oocyte cryopreservation is a feasible FP option for AYAs who may not have other alternatives when appropriate precautions are taken, such as proper counseling and having a support team. These promising outcomes correspond to similar findings of recent small case series, providing hope for these patients to have genetically related offspring in the future.

Introduction

Infertility is predicted to affect up to 186 million individuals worldwide [1]. The adolescent and young adult (AYA) population can be affected by a number of gonadotoxic threatening diseases resulting in impaired fertility. Although cancer diagnoses and some subsequent therapies are commonly thought of as leading fertility insults, other nonmalignant diseases/conditions such as rheumatic or hematologic diseases leading to bone marrow transplantation, gender dysphoria, Turner’s syndrome, as well as others can also be detrimental to the gonads [2–5].

Many young cancer patients have reported that not having biological children of their own in the future is a significant concern [6–9] and future infertility has been documented as a source of stress, depression, and anxiety [10–13]. Though limited data is available, some studies have also shown data regarding transgender youth and the desire to have genetically related offspring [4, 14]. However, this population tends to have a higher interest in many types of family building options, but also studies revealed that when questioned, ~50% noted a possibility of desiring genetically related offspring in the future, although they currently did not have that desire [14, 15]. While exceedingly rare, declining chemotherapy out of fear of future infertility has been reported in young cancer patients [16]. Implementation of fertility preservation (FP) counseling as a key component of disease treatment has helped decrease decisional regret and anxiety over potential decline in fertility and supported by survivors and their parents/guardians [7, 10, 17–20]. When considering FP options, the age of the individual, pubertal status, underlying medical condition and/or comorbidities, cultural background, ethical concerns, and partner status should be factored into the decision [3].

Chemotherapy drugs and radiation therapy can often lead to undesirable side effects for younger patients such as subfertility and infertility. These therapies are not only utilized by AYAs with cancer diagnoses, but those with nonmalignant conditions, such as vasculitis, certain renal diseases, and systemic lupus erythematous, have also been exposed to gonadotoxic levels of alkylating agents [5, 21, 22]. Additionally those with severe hemoglobinopathies requiring stem cell transplantation are also at risk of future infertility [5, 23]. Other vulnerable populations impacted by fertility concerns include those with various congenital/genetic conditions (fragile X syndrome, Turner’s syndrome, cystic fibrosis, etc.) and those with gender dysphoria who may have been exposed to gender-affirming therapies [5, 24]. There has been an increase in the use of FP, which is the freezing of gametes or reproductive tissue, prior to gonadotoxic therapies for malignancies and other disorders that place patients at high risk for future infertility and premature ovarian failure [25–32]. Recent improvements in vitrification and thawing techniques have made preserving oocytes after controlled ovarian hyperstimulation (COH) an increasingly viable FP option for young patients or those without a partner [33–36], and experimental alternatives such as ovarian tissue cryopreservation (OTC) exist for prepubertal patients and patients uninterested in undergoing COH prior to disease treatment [37–44].

FP has been identified as a key issue for young survivors and other affected AYA by the American Society of Clinical Oncology (ASCO), the American Academy of Pediatrics (AAP), and the American Society of Reproductive Medicine (ASRM) [3, 45–47]. While multidisciplinary coordination and disease treatment strategies including FP have been developed [5, 48–51], there may be some ethical concerns regarding FP in pediatric patients [23, 52–54]. Among these concerns are efficacy of FP techniques in younger patients (specifically the prepubertal population), differences in comfort levels, and opinions of physicians implementing experimental techniques [55]. Additionally, there are ethical concerns surrounding disposition of cryopreserved oocytes or embryos resulting from FP procedures. While many reports regarding disposition outcomes in the adult population exist, they are very few regarding oocyte and/or embryo disposition in the AYA population. In light of vague medical society guidelines that do not delineate circumstances that are ethically permissible for adolescent and especially prepubertal FP, there is a tremendous amount of variety in physician attitudes even some restrictions set in hospitals themselves [54].

Physicians that find adolescent FP ethically permissible may still hesitate to initiate COH based on lack of large cohort studies detailing adolescent ovarian stimulation outcomes [56–59]. There are few studies that detail complications, delay in initiating time-sensitive disease treatment, and pregnancies and/or live births years after the completion of treatment. One study described comparable stimulation outcomes in eight 14–18-year-old sickle-cell anemia (SCA) patients that underwent hematopoietic stem cell transplantation (HSCT) but also noted that one patient was admitted to the hospital for moderate ovarian hyperstimulation [23]. Live birth from oocytes vitrified during teenage years has also been reported [33]. Additionally, discontinuation of testosterone treatment and increased estradiol (E₂) levels from COH present an increased risk of gender dysphoria and incongruence for transgender persons [60]. The goal of this study is to describe the multidisciplinary approach and report stimulation outcomes as well as disposition outcomes in AYA patients who underwent oocyte cryopreservation for FP.

Materials and methods

Study population

This was an IRB approved, multi-site retrospective study. Subjects were identified from oocyte retrieval patient logs. Specifically, we examined women aged between 13 and 21 years that froze oocytes after COH at Northwestern Medicine Fertility and Reproductive Medicine clinic and Michigan Medicine’s Center for Reproductive Medicine from January 2007 through January 2018. Subjects were excluded if they were older than 21 years at the time of presentation to each respective clinic or if they were being treated for something other than FP. For each patient, diagnosis prompting FP, age, BMI, and COH data were collected. Patients were stratified into two age groups for analysis: 13 to 17 years and 18 to 21 years.

Multidisciplinary coordination

The initial appointment with the reproductive endocrinology department was coordinated by the patient navigator. The role of the patient navigator is critical, as this individual assists in quickly maneuvering patients through a time-sensitive process. The patient navigator guides the patients and their families through the healthcare system, which at times can be complex, ensures efficient consult completion, ensures continued patient/family engagement, and assists in coordinating appointments and FP procedures. A patient navigator may also assist in identifying families that have financial need and connect them with resources to help cover costs associated with FP procedures [5, 54, 61]. All patients at one institution met with a psychologist or social worker to ensure that they understood the risks and benefits of undergoing COH, as well as the probability of future pregnancy from frozen oocytes after surviving disease treatment. Patients at the other institution are offered these services, but they are not mandated. At both institutions, patients <18 years gave assent in addition to written consent from the parents or guardians. Transabdominal ultrasound monitoring was available for those that could not tolerate vaginal exams. Anesthesiologists who were comfortable sedating minors were also part of the treatment team.

Controlled ovarian hyperstimulation

Our protocol has been documented in previous studies [62, 63]. Briefly, COH was started using recombinant follicle stimulating hormone (FSH) with or without urinary menotropins with dosage based on age and ovarian reserve measurements. Over time, our practice has evolved to include more random start (RS) protocols, meaning that patients who desire to begin stimulation immediately can do so. For a cycle-specific (CS) protocol, gonadotropins were initiated on the third day of menses, whereas for a RS protocol, gonadotropins were initiated at any point in the menstrual cycle. Response to medication was evaluated with regular ultrasounds (either transvaginal or transabdominal, depending on patient’s comfort level with vaginal exams) and E₂ measurements, with gonadotropin dosage adjusted accordingly. For a CS protocol, once the leading follicle grew to at least 12 mm in diameter or E₂ reached 300 pg/mL, the patient began a daily injection of gonadotropin-releasing hormone (GnRH) antagonist to prevent ovulation. For RS, antagonist was started once the new lead follicle grew to at least 12 mm. Starting gonadotropin dose was determined by anti-Müllerian hormone (AMH) and/or antral follicle count (AFC). According to the institutional IVF protocols for all patients, when at least three follicles measured 16 mm or greater in diameter, final follicular maturation was triggered by an injection of human chorionic gonadotropin, and oocyte retrieval was performed 36 h later. Oocyte retrieval was achieved with transvaginal ultrasound guidance in all patients. Slow cooling was used for oocyte cryopreservation until 2008, when vitrification became standard protocol.

Oocyte disposition

Prior to undergoing COH, each patient was asked to document their preferred disposition of their oocytes if they were to unfortunately pass away prior to use. The following options were offered: discard all oocytes, donate oocytes to research, or choose an individual to use oocytes to initiate pregnancy. The final decision was documented and signed on an intake form, usually during the patient’s initial visit.

Statistical methods

Data were analyzed using chi-square tests to compare categorical variables, t-tests to compare continuous variables, and one-way ANOVA tests for comparisons between multiple groups. Subsequently, linear and logistic regression analyses were performed to adjust for potentially confounding variables. Statistical analyses were performed with SPSS IBM Statistics 25.0 for Windows (SPSS, Chicago, IL). All p values were two-sided, and a p value of < 0.05 was considered statistically significant.

Results

A total of 41 AYA patients began stimulation, and 38 completed a COH cycle, of which 36 froze oocytes and 2 froze embryos with a partner, for FP between the years 2007 and 2018, and were included in the analyses (Table 1). Out of the 38 who completed a cycle, 14 (36.68%) were ages 13 to < 18 years, and 24 (63.16%) were ages 18 to < 21 years. The frequency distribution of ages for each cohort is displayed in Fig. 1. The most common diagnosis for patients was cancer (total n = 22; n = 6 were recurrent cancer), followed by noncancerous disorders (total n = 16; n = 5 were hemoglobinopathies, specifically beta thalassemia n = 2, SCA n = 1, aplastic anemia n = 1, and paroxysmal nocturnal hemoglobinuria n = 1; remaining specific diagnoses were gender dysphoria (n = 5), Turner’s syndrome (n = 2), panhypopituitarism, NMDA autoimmune encephalitis, multiple sclerosis, and benign dermoid cyst, each with an n = 1). A total of 3 patients began ovarian stimulation but were canceled for poor response (primary malignancy n = 1, recurrent malignancy n = 1, nonmalignant disease n = 1 (diagnosis of primary ovarian insufficiency)). All remaining patients successfully completed COH and oocyte retrieval, with mature oocytes obtained and cryopreserved without any adverse outcomes.

Table 1.

Demographic characteristics of AYA patients who initiated an oocyte retrieval

Demographic Measures (n=41)	<18 years old (n=16)	≥18 years old (n=25)
Cancelled cycle (n)	2	1
Age
Median (Range)	15.57 (13.00-17.81)	19.27 (18.00-20.96)
BMI
Median (Range)	23.31 (19.14-36.02)	22.11 (15.72-47.50)
AMH
Median (Range)	2.54 (0.08-6.50)	1.95 (0.13-7.36)
Peak E2
Median (Range)	1446 (103-3469)	1361 (25-4252)

No significant difference observed between all measures except for age

AMH anti-Müllerian hormone; AYA adolescent and young adult; BMI body mass index; E₂ estradiol

Fig. 1.

AYA study subject demographics by age group

When dividing the groups by ages < 18 years old and ≥ 18 years old, the median doses of FSH used were 2325 and 2038 IU (NS), the median number of mature oocytes retrieved were 10 (NS), and median number frozen oocytes were 11 and 13 (NS), respectively (Table 2A). The median days of stimulation were 10, and median number of total oocytes retrieved was 13 for both groups (NS, Table 2A). There was no statistical difference in BMI, AMH, peak E₂, total FSH dosage, total HMG dosage, days stimulated, total oocytes retrieved, mature oocytes retrieved, and oocytes frozen between the two groups (Table 2A). When separating the groups by diagnoses of malignancy, recurrent malignancy, and nonmalignant disease, there was no statistically significant difference in stimulation outcomes among the measured parameters, although among certain diagnoses, there was a trend toward significance (Table 2B). Of note, AMH was lower in the recurrent cancer group (Table 2B). When dividing the groups by history of chemotherapy prior to stimulation, subjects that had previously undergone chemotherapy had significantly lower AMH (0.60 vs. 2.32; p = 0.032), lower total oocytes retrieved (6 vs. 13; p = 0.015), lower mature oocytes retrieved (4 vs. 12; p = 0.003), and lower oocytes cryopreserved (4 vs. 13; p = 0.049) (Table 2C). There were no cases of ovarian hyperstimulation syndrome (OHSS), and no complications from the stimulation or retrieval were noted.

Table 2A.

COH cycle characteristics of AYA patients who completed an oocyte retrieval by age groups

Stimulation Measures (n=38a)	<18 years old	≥18 years old	p-value
Number of Subjects (n)	14	24
Subjects with history of chemotherapy (n)	2	7
AMH (ng/ml)
Median (Range)	2.72 (0.25-6.50)	2.00 (0.13-7.36)	0.505
Peak E2 (pg/ml)
Median (Range)	1465 (302-3469)	1422 (363-4252)	0.855
Number of days of stimulation
Median (Range)	10 (8-15)	10 (8-15)	0.749
Total FSH Dosage (IU)
Median (Range)	2325 (0-3375)	2038 (525-5850)	0.889
Total HMG Dosage (IU)
Median (Range)	750 (0-3375)	750 (0-2700)	0.930
Total number of oocytes retrieved
Median (Range)	13 (4-31)	13 (2-37)	0.872
Number of mature oocytes
Median (Range)	10 (0-25)	10 (2-22)	0.981
Number of oocytes cryopreserved	n=14	n=22
Median (Range)	11 (1-28)	13 (2-27)	0.949
Number of embryos cryopreserved	n=0	n=2
Median (Range)		3.5 (3-4)

No significant differences were observed between groups

a: n = 3 low-response cancelations, of which n = 2 were < 18 years old

AMH anti-Müllerian hormone; AYA adolescent and young adult; COH controlled ovarian hyperstimulation; E₂ estradiol; HMG human menopausal gonadotropin

p values determined by independent samples t-test

Table 2B.

COH cycle characteristics of AYA patients who completed an oocyte retrieval grouped by diagnosis

Stimulation Measures (n=38a)	Primary Malignancy	Recurrent Malignancy	Other Reason	p-value
Number of Subjects (n)	16	6	16
Subjects with history of chemotherapy (n)	3	5	1
AMH (ng/ml)
Median (Range)	2.10 (0.20-6.63)	0.90 (0.13-2.10)	3.41 (0.25-7.36)	0.137
Peak E2 (pg/ml)
Median (Range)	1450 (363-4252)	1295 (669-1484)	1763 (302-3769)	0.534
Number of days of stimulation
Median (Range)	10 (8-15)	12 (9-13)	10 (8-15)	0.144
Total FSH Dosage (IU)
Median (Range)	2212 (0-5850)	2813 (1650-3075)	2150 (1050-3375)	0.298
Total HMG Dosage (IU)
Median (Range)	1088 (0-2700)	1013 (0-1800)	675 (0-3375)	0.192
Total number of oocytes retrieved
Median (Range)	14 (2-37)	8 (3-18)	13 (4-30)	0.129
Number of mature oocytes
Median (Range)	11 (2-25)	6 (2-10)	12 (0-23)	0.067
Number of oocytes cryopreserved	n=15	n=5	n=16
Median (Range)	12 (2-27)	6 (3-18)	13 (7-28)	0.194
Number of embryos cryopreserved	n=1	n=1	n=0
Median (Range)	4	3

No significant differences were observed between groups

a: n = 3 low-response cancelation, n = 1 from each group

AMH anti-Müllerian hormone; AYA adolescent and young adult; COH controlled ovarian hyperstimulation; E₂ estradiol; HMG human menopausal gonadotropin

p values determined by Kruskal-Wallis H test

Table 2C.

COH cycle characteristics of AYA patients who completed an oocyte retrieval by history of chemotherapy

Stimulation Measures (n=38a)	No history of chemotherapy	History of chemotherapy	p-value
Number of Subjects (n)	29	9
Age
Median (Range)	18.30 (13.00-20.76)	18.78 (15.00-21.00)	0.638
AMH (ng/ml)
Median (Range)	2.32 (0.20-7.36)	0.60 (0.13-3.50)	0.032
Peak E2 (pg/ml)
Median (Range)	1539 (302-3769)	1256 (363-4252)	0.186
Number of days of stimulation
Median (Range)	10 (8-15)	12 (8-15)	0.210
Total FSH Dosage (IU)
Median (Range)	2175 (0-3300)	2925 (525-5850)	0.114
Total HMG Dosage (IU)
Median (Range)	750 (0-2700)	1275 (0-3375)	0.741
Total number of oocytes retrieved
Median (Range)	13 (5-31)	6 (2-37)	0.015
Number of mature oocytes
Median (Range)	12 (4-25)	4 (0-22)	0.003
Number of oocytes cryopreserved	n=29	n=7
Median (Range)	13 (5-28)	4 (1-27)	0.049
Number of embryos cryopreserved	n=0	n=2
Median (Range)		3.5 (3-4)

a: n = 3 low-response cancelations, of which n = 2 had history of chemotherapy prior to stimulation

AMH anti-Müllerian hormone; AYA adolescent and young adult; COH controlled ovarian hyperstimulation; E₂ estradiol; HMG human menopausal gonadotropin

p values determined by independent samples t-test

For oocyte/embryo disposition elected at the time of cryopreservation, 63.4% (n = 26) of patients chose to donate to research, 26.8% (n = 11) to donate to a person of their choosing, and 4.9% (n = 2) to discard (n = 2 unavailable) (Table 3).

Table 3.

Disposition selection of oocytes

	<18 years old (n=16)	≥18 years old (n=25)
Discard all oocytes	1 (6.30%)	1 (4.00%)
Donate to research	11 (68.80%)	15 (60.00%)
Selected individual	3 (18.80%)	8 (32.00%)
Not noted	1 (6.30%)	1 (4.00%)

Discussion

An ideal FP option for young female adults is one that can be applied to those who are single or not in a committed relationship. Therefore, COH with oocyte cryopreservation is a reasonable option to consider in this population. To our knowledge, this is the largest multicenter cohort demonstrating the safety profile of COH in the AYA population desiring FP for both oncology-based and non-oncology-based diagnoses. In our study, we divided age groups based on the suspected maturity of the hypothalamic-pituitary-ovarian (HPO) axis, as it is anticipated that many females < 18 years of age may have an immature HPO axis. Therefore, our two cohorts compared were ages 13 to < 18 years and ≥ 18 to 21 years old. Most patients in this study successfully underwent COH and oocyte retrieval, resulting in the collection and cryopreservation of mature oocytes without the occurrence of any adverse outcomes. Our younger patients (< 18 years old) did require higher doses of gonadotropins and froze fewer oocytes, likely attributed to the immaturity of the HPO axis, but these differences were not statistically significant. There were no statistically significant differences in the other parameters measured, which included BMI, AMH, peak E₂, and days stimulated.

There are many concerns about FP among an adolescent population. Some issues that may arise include multiple parental concerns regarding the safety and complexity of the procedure, parent decision-making on behalf of the patient, adolescent decision capacity, the use of experimental options in certain populations, and the decision on what to do with the gametes if there is an untimely death of the patient [5]. For these reasons, we think that having a psychologist and or social worker as part of the team is crucial. At times, this decision could be difficult for the parents/guardians due to religious and cultural views on sexuality and concerns for loss of virginity due to the transvaginal approach during oocyte retrieval [23]. Although these concerns can be challenging to address, it should not inhibit or preclude offering COH as an FP option to the AYA population. It also provides an opportunity for patient and parental education.

Since FP in adolescent patients introduces complex challenges, a multidisciplinary approach should be taken when caring for this population. This includes performing appropriate pre-procedure counseling and having a support team in place. In our study, an integrative team was involved in providing care and support to our young adult patients. Our group consisted of a patient navigator, REI clinicians comfortable with the use of COH protocols in adolescents, psychologists or social workers, nursing staff, and anesthesiologists that were comfortable sedating minors. For those patients not comfortable with vaginal exams, a transabdominal ultrasound was performed to assess AFC as well as to monitor response to gonadotropins. Although studies have suggested that transabdominal ultrasound may decrease the accuracy of AFC, overall this did not pose a significant issue in our patient population and has previously been successfully used for monitoring in similar populations [23, 64–66]. Even in patients who had monitoring performed transabdominally, the oocyte retrieval was accomplished transvaginally without any issues.

There have been several previously published studies evaluating outcomes with COH in the AYA population; however, the majority of them tend to be small case reports or case series [23, 64, 65, 67]. Larger studies do exist, but there are still conflicting reports regarding safety and outcomes. The largest published study to date is a recent study by Hipp et al. using data from the SART CORS database [68]. In this study, a de-identified file released from SART CORS was analyzed; thus, there could be omitted or missing data and other details or minor complications that would not necessarily be reported. Additionally, more specific details of the patients included would not be available (i.e., type of cancer or reason for FP, etc.) [68].

We found that overall ovarian stimulation was well tolerated with no adverse side effects. Similar to our study, one recently published prospective study in Sweden consisting of 24 adolescent females (ages 14–17 years) demonstrated safe and successful oocyte cryopreservation in this population [69]. Live birth rates of 54% and 46% were demonstrated with the use of cryopreserved embryos and cryopreserved oocytes, respectively. Utilization rates among those individuals of childbearing age who were still alive at time of follow-up were 29% and 8% for embryos and oocytes, respectively [69]. In our patient cohort, none of the patients have returned to use their gametes.

Although several reports exist regarding the oocyte/embryo disposition selection in the adult population, the data regarding this in the adolescent population is limited. In our study, the selected options for oocyte disposition included discarding all oocytes, donating to research, and selecting an individual to allow to use and to initiate pregnancy or were not noted/unavailable in the patient record (Table 3). There was only a small difference in the selected disposition preference when comparing the younger cohort to the older cohort. The most notable difference was that fewer subjects from the < 18-year-old group chose to select an individual to use their oocytes in the case of death of the patient.

There have been concerns regarding safety of COH in the adolescent population. Pecker et al. demonstrated serious complications related to SCA in young women (ages 15–32 years) who underwent various FP strategies, which included COH using the antagonist protocol [70]. Some of the complications experienced were pre-procedural, requiring the stimulation cycle to be postponed, while others experienced postharvest painful crisis [70]. Another study reported one patient who experienced a moderate case of OHSS, requiring hospital admission and supportive care [23]. We did not experience any of these adverse outcomes in our patient population. One option to limit the risk of OHSS may be to have a low threshold for considering use of a GnRH agonist trigger instead of hCG. However, there are concerns using GnRH agonists in the adolescent population due to lack of the maturity of the HPO axis [65]. Therefore, it is imperative to check serum progesterone and luteinizing hormone (LH) levels ~ 8–14 h following a GnRH agonist trigger to ensure that the GnRH trigger was effective [71, 72] (typically an inadequate response is defined as a progesterone < 3 ng/ml and an LH < 15 IU/L [72].) To determine the true efficacy of the use of a GnRH trigger in this population, more large studies would need to be completed. Several years ago, a novel concept of a double trigger, combining a GnRH agonist and hCG administration 40 and 34 h, respectively, prior to oocyte retrieval in those women with a high proportion of immature oocytes was found to improve outcomes [73]. However, there is lack of evidence of use of this protocol in the AYA population; thus, further studies are needed.

The main strength of this study is that it is one of the few larger studies demonstrating the efficacy and safety of COH as an FP option in the AYA population, thus providing a resource to other providers when considering FP options in this patient population. However, the main limitation is that it is a retrospective investigation, which poses inherent issues. It is possible that outcome data may be lacking. Additionally, selection bias may exist when comparing patients who pursue FP with those who do not, especially within the oncology population as those who are healthier may be more willing to delay treatment for the cancer and purse fertility options. There were also patients in our cohort who had undergone chemotherapy prior to COH, which resulted in statistically significant differences in AMH and oocytes retrieved (Table 2C). Finally, because cryopreserved gametes are stored at a long-term storage facility and we are studying a population that is remote from the age in which they will utilize them, it is difficult to plan for longer-term follow-up studies to determine use of gametes and pregnancy outcomes.

Taken together, the results of this study demonstrate that COH and oocyte cryopreservation are a safe and feasible FP option for AYA patients who may not have other alternatives if a multidisciplinary team approach and appropriate precautions are taken. Future studies should focus on developing multicenter nationwide databases that are compliant with HIPAA and research safety guidelines but could allow for prospectively following these patients, thus providing the most definitive answers regarding long-term reproductive outcomes. Our study agrees with several other small studies and case reports and offers a safe option for this patient population to have genetically related offspring in the future.

Funding Information

This study is supported by the Northwestern Memorial Foundation Evergreen Grant (to MEP) and P50 HD076188 (MEP, PI: T. Woodruff).