Oocyte Cryopreservation For Fertility Preservation Research Articles

Effect of Educational Program on Knowledge, Attitudes, and Intention of Unmarried Healthy Females regarding Oocyte Cryopreservation for Fertility Preservation

Effect of Educational Program on Knowledge, Attitudes, and Intention of Unmarried Healthy Females regarding Oocyte Cryopreservation for Fertility Preservation

P-677 Letrozole inhibits ovulation via reducing responsiveness to luteinizing hormone in in vitro-grown mouse follicles

Abstract Study question Does letrozole reduce responsiveness to luteinizing hormone (LH) in in vitro-grown mouse follicles? Summary answer We found that letrozole reduced responsiveness to LH via reducing of luteinizing hormone/chorionic gonadotropin receptor (Lhcgr) transcription in in vitro. What is known already The continuous dosing of letrozole, the third-generation aromatase inhibitor, is used for the controlled ovarian stimulation (COS) of fertility preservation cycles in women with hormone-sensitive breast cancer to prevent the transient rise of serum estrogen levels. Recently, lower oocyte maturation rates and higher abnormal fertilization rates in COS with letrozole compared to standard COS have been reported. The studies using aromatase knockout mice and estrogen receptor beta knockout mice showed that intra-follicular estrogen is essential for responsiveness to LH of granulosa cells. However, whether letrozole reduces responsiveness to LH of follicles remains unknown. Study design, size, duration We evaluated the effect of letrozole on responsiveness to LH using in vitro mouse follicle culture system. Preantral follicles (150-200 µm) with a small number of stromal cells were isolated from 3 weeks old C57BL/6jjcl mouse ovaries and cultured in the presence of letrozole. We analyzed in vitro ovulation ability, and expression levels of ovulation-related genes to clarify the effect of letrozole on responsiveness to LH of follicles. Participants/materials, setting, methods The follicles were cultured with letrozole (0.01µM, 0.1µM, or 1µM) or vehicle (0.1% DMSO) for 5 days followed by 5 IU/ml hCG and 5 ng/ml hEGF stimulation as ovulation induction. The diameter and survival rate of follicles were assessed. After16 hours after ovulation induction, we assessed the ovulation and measured the transcription of Lhcgr, Ptgs2, Runx1 and Actb (internal control) in the follicles by RT-qPCR. We conducted a collateral experiment in the presence of estradiol. Main results and the role of chance The follicle growth and survival rate did not change by letrozole in vitro. However, in vitro ovulation was reduced by the addition of letrozole in a dose-dependent manner (Cochran-Armitage trend test, P < 0.0001): 41.2% in the 0.01µM letrozole treated group (n = 23), 10.5% in the 0.1µM letrozole treated-group (n = 17), and no ovulation in the 1µM letrozole treated-group (n = 19) compared with 69.6% in the vehicle-group (n = 18). Exogenous estrogen addition restored the ovulation ability of 1µM letrozole-treated follicle to the same levels as the vehicle group. RT-qPCR revealed that 0.1 µM letrozole significantly reduce the transcription levels of Lhcgr (P = 0.0027), Runx1 (P = 0.0124), and Ptgs2 (P = 0.0067) compared with vehicle-treated follicles. Exogenous estrogen addition restored the transcription of these genes to levels observed in vehicle-treated follicles. We also observed a positive correlation between the transcription of Lhcgr and Ptgs2 (R = 0.55, P = 0.0003), Lhcgr and Runx1 (R = 0.71, P < 0.0001), and Ptgs2 and Runx1 (R = 0.77, P < 0.0001). Our results suggested that letrozole-treated follicles impaired ovulation due to dysregulation of Lhcgr transcription and its downstream cascade caused by estrogen deficiency. Limitations, reasons for caution This is an in vitro experiment using a mouse model. Further research is needed to determine whether our findings are applicable to humans. Wider implications of the findings Our findings imply that letrozole may have disadvantages in not only ovulation, but also subsequent reproductive processes affected by the effectiveness of the LH surge, such as oocyte maturation, fertilization, and preimplantation embryo development. When evaluating oocyte cryopreservation for fertility preservation, it may be necessary to consider the COS protocol. Trial registration number Not applicable

O-278 Medical and ethical perspectives of performing ovarian stimulation and oocyte cryopreservation for fertility preservation (FP) in adolescents: 5 years’ experience from a tertiary centre

Abstract Study question What are the medical and ethical challenges of performing ovarian stimulation and oocyte cryopreservation in adolescents and what are the barriers to provision? Summary answer Oocyte cryopreservation for benign and malignant indications in adolescents is associated with unique medical and ethical challenges. What is known already An improvement in childhood cancer survival, increased transgender care and benign conditions such as haemoglobinopathies requiring stem cell transplant have led to higher representation of adolescent birth-registered females in FP clinics. FP in adolescents has increased complexities, both physical (pubertal stage, diagnosis) and psychological (accepting diagnosis, processing information, decision-making). Concerns relate to reliability of AMH in adolescents, anticipated response to ovarian stimulation and oocyte quality. Counselling and consenting young people and their families about fertility decisions, often alongside receiving a life-changing diagnosis, is an ethically complex area. Assessing capacity to consent is not straightforward. We report our clinical experience. Study design, size, duration This was a retrospective, observational cohort study of 26 adolescent birth-registered females aged 13 to 18 years who underwent ovarian stimulation and oocyte cryopreservation in a specialist unit for fertility preservation between 2018 and 2022. The primary outcome was oocyte yield, secondary outcomes included complications and drop-out rate. Participants/materials, setting, methods We included post-pubertal adolescent birth-registered females aged 13 to 18 years who were referred for fertility preservation for high risk of gonadotoxicity from treatment and who commenced ovarian stimulation for oocyte cryopreservation. Data was retrieved from a prospectively managed database. We noted demographic data, ovarian reserve, method of monitoring, response to ovarian stimulation and oocyte cryopreservation and route of egg collection. Documentation on counselling conversations and psychological maturity was retrieved from clinical records. Main results and the role of chance There were a total of 29 ovarian stimulation cycles performed in 26 adolescent birth-registered females aged between 13 and 18 years. Indications for fertility preservation included malignancy 62% (16/26), immunological disorders 19% (5/26), gender reassignment treatment 8% (2/26), recurrent ovarian cyst surgery 8% (2/26) and benign haematological disease 4% (1/26). The youngest was aged 13 years and 10 months at the time of egg collection. Minimum time from menarche to ovarian stimulation was 11 months. 23% (6/26) adolescents had previously received chemotherapy. AMH was 2.8-37 pmol/L and AFC 2-36. AFC correlated well with AMH in the majority. Random-start was performed in 54% (14/26) and dual stimulation in 12% (3/26). Number of cryopreserved oocytes was 3-45 and number of MII oocytes cryopreserved 3-35. Ultrasound monitoring was performed transabdominally in 88% (23/26) and transvaginally in 12% (3/26). Egg collection was performed transvaginally in all cases in this cohort, comprising adolescents from varying ethnicities. All cycles proceeded to completion. There were no complications in any cycle, including the 42% (11/26) performed for haematological malignancy. All adolescents were counselled in association with a family member to obtain informed consent. All were assessed as able to comprehend discussions. Limitations, reasons for caution There is limited data on performing oocyte cryopreservation in adolescents. Further studies expanding on our findings are needed to support clinicians to perform oocyte cryopreservation in this population. Concerns remain regarding increased aneuploidy rates in this age group compared to women in their 20s. Livebirth outcome data is needed. Wider implications of the findings This is the largest case series to date. Post-pubertal adolescents as young as age 13 can undergo ovarian stimulation and oocyte cryopreservation. Transvaginal egg collection is an accepted procedure when counselled appropriately. Clinician experience, correct setting and funding enable a permissive environment for oocyte cryopreservation in this population. Trial registration number N/A

Outcomes of Different In Vitro Maturation Procedures for Oocyte Cryopreservation for Fertility Preservation and yet Another Live Birth in a Cancer Patient.

To ensure patient care in an oncological fertility preservation (FP) programme, specialists must provide technology that best suits the patients' clinical conditions. In vitro oocyte maturation (IVM) and ovarian tissue cryopreservation (OTC) are possible fertility preservation treatments for women in need of urgent oncological treatment. IVM consists of the retrieval of immature oocytes from small antral follicles, with no or minimal ovarian stimulation by gonadotropins. Therefore, IVM has become a pertinent option for fertility preservation, especially for cases whereby ovarian stimulation is unfeasible or contra-indicated. Existing data on immature oocytes, retrieved transvaginally (OPU-IVM) or extracted from ovarian tissue 'ex vivo' (OTO-IVM), are still limited on technical consistency, efficacy, and safety. The present retrospective cohort study includes 89 women undergoing fertility preservation using IVM methodologies and 26 women undergoing ovarian stimulation (OS) in concomitant period. In total, 533 immature oocytes were collected from IVM patients, achieving a maturation rate of 57% and 70% in OTO-IVM and 73% and 82% in OPU-IVM at 24 h and 48 h in culture, respectively. The observed high maturation rates might be due to the use of patients' serum in its innate status, i.e., without heat-inactivation. This permitted 7.6 ± 5.7 and 4.6 ± 4.9 oocytes to be vitrified in OTO-IVM and OPU-IVM, respectively, compared to 6.8 ± 4.6 from OS patients. Regarding OS patients, two of them underwent embryo transfer following the insemination of warmed oocytes after complete remission, resulting in a single live birth from one patient. Upon follow-up of two OTO-IVM patients after the termination of their oncological treatment, a total of 11 warmed oocytes lead to a transfer of a single embryo, but pregnancy was not achieved. From OPU-IVM, six embryos were transferred in three patients 4.25 years after oocyte vitrification, leading to the live birth of a healthy boy. The present case of live birth is among the first cases reported so far and supports the notion that IVM might be a relevant and safe FP option for cancer patients when oocyte preservation is required but ovarian stimulation is contra-indicated.

Oocyte vitrification for oncological and social reasons.

The aim of this review is to present information related to oocyte cryopreservation, and particularly oocyte vitrification, performed to preserve fertility in oncologic and social indications. The success rates of oocyte cryopreservation have increased with the widespread use of the vitrification technique and are currently similar to those of in vitro fertilization performed with fresh oocytes. Vitrification is the most successful technique for oocyte cryopreservation. The most important factors that influence the success rate are the patient's age at the time of vitrification and the number of mature oocytes frozen. Thus, live birth rates differ for each age depending on the number of oocytes thawed and the freezing method. The American Society of Reproductive Medicine and the American Society of Clinical Oncology recommend presenting the option of oocyte cryopreservation for fertility preservation in cancer patients. Besides cancer patients, use of oocyte vitrification is increasing in women who wish to postpone pregnancy age and to have reproductive freedom with the development of the cryopreservation technique and the achievement of pregnancy rates similar to the use of fresh oocytes. Patients are provided consultancy service in terms of indication, the success rates by age, and the total number of oocytes frozen. It should be emphasized that this procedure is not a type of insurance policy for fertility, especially in elective oocyte cryopreservation.

P-476 Why are they not coming back? A single-center follow-up study on oncological women oocyte's storing for fertility preservation

Abstract Study question Which is the return rate and which factors are responsible for the non-return in cancer patients who underwent oocyte cryopreservation for fertility preservation? Summary answer Return rate was 11.7%. Young age at freezing, lack of a partner and type of cancer were the main factors responsible for the non-return. What is known already Improvements in oncological early diagnoses and therapies have significantly increased the survival rates of patients, allowing clinicians to focus on long-term quality-of-life issues, such as access to motherhood. An extensive literature on the importance of fertility preservation (FP) has been produced thanks to the growing number of patients undergoing FP cycles over the years. Nevertheless, the rates of patients returning to use their cryopreserved material have shown to be considerably low, ranging from 5 to 8%. Significant data regarding the reasons that might explain such low return rates are still scarce. Study design, size, duration This is a single-center follow-up retrospective study that includes all women who underwent oocyte cryopreservation cycles for oncological purposes at referral University affiliated center, from January 2001 to December 2017. Participants/materials, setting, methods The database consists of 171 patients, among those 110 (64%) were diagnosed with breast cancer, 45 (26%) hematological cancer, 5 (3%) gynecologic cancer and 11 (7%) other cancers. Data about returned patients were retrieved from internal registries. Non-returned patients were assessed by standardized phone survey on health and marital status, family projects, spontaneous conceptions, and reasons why they had not returned to use their gametes. A univariate analysis between returned and non-returned patients was performed. Main results and the role of chance Among the 171 women who underwent oocyte cryopreservation, 9 (5%) died and 17 (10%) were lost at follow up. In the remaining 145-patient group, the mean age at freezing was 32.2±6.1 and at follow-up 38.2±6.7 years. A total of 20 patients (11.7%) returned to use their frozen material and 125 did not. In the non-returned group, 37 (29.6%) did not have a partner, 10 (8%) had a previous spontaneous conception and 15 (12%) had recurrent malignancy at the time of follow-up. In the univariate analysis, younger age at freezing (31.8±6.2 vs 35.2±4.7; p 0.018), lack of a partner (p 0.002), type of cancer (other than breast cancer; p 0.024) were the significant factors in the non-returned group. As for the personal reason for not coming back, patients mainly answered as follows: lack of a partner (29, 23.2%), desire of spontaneous motherhood (24, 19.2%), previous spontaneous pregnancies after FP procedures (16, 12.8%), and still ongoing hormonal therapy for breast cancer (13, 10.4%). Nonetheless all of them confirmed their will to keep the storage of their oocytes. Limitations, reasons for caution The study population consists of a limited number of patients from a single Italian Fertility Center. Since the Italian law limits ART access to heterosexual couples, this setting may limit any possible adaptation of the study to other countries, with different legislations. Wider implications of the findings The impact of a cancer diagnosis on a woman’s maternal desire, sentimental status and life priorities should be studied more thoroughly. Moreover, it is important to encourage studies investigating so long hormonal therapy suppression in breast cancer patients seeking pregnancy in order to reduce their time to pregnancy. Trial registration number na

Planned oocyte cryopreservation for fertility preservation

Background: Oocyte cryopreservation opens up opportunities for women to preserve fertility when it is necessary to postpone pregnancy. After the advent of vitrification, the results of oocyte cryopreservation were significantly improved compared to conventional slow-freezing. Through these improvements, oocyte cryopreservation was introduced to overcome a decline in fecundity due to an increase in age, and this modality is defined as planned oocyte cryopreservation.Current Concepts: Oocytes cryopreserved through vitrification appear to result in similar clinical pregnancy rates and live birth rates compared to fresh oocytes, though the evidence is still limited. It has been reported that the live birth rate increases when the planned oocyte cryopreservation is performed at a younger age. Obstetrical and neonatal outcomes appear similar between vitrified and fresh oocytes.Discussion and Conclusion: Preliminary data supports planned oocyte cryopreservation as a feasible modality resulting in fertility preservation and subsequent live births. The fact that performing the procedure at a younger age can increase the oocyte yield, oocyte efficacy, and live birth rate can be discussed along with patient consultation. However, as there is still a lack of data on the standardized live birth rate, the number of oocytes to be collected, and the long-term effect on the children; more well-designed studies are needed to improve counseling and decision-making in patients seeking this treatment.

Disposition preferences in oocyte preservation patients.

To characterize the frozen oocyte disposition preferences of patients undergoing medical and planned fertility preservation. 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. A total of 336 OC patients with a documented oocyte disposition preference were identified in the study timeframe. Patients were on average 34.5years 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). 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.

The use of oocyte cryopreservation for fertility preservation in patients with sex chromosome disorders: a case series describing outcomes.

Characterize outcomes among adolescents and young adults (AYAs) with sex chromosome disorders (SCDs) after oocyte cryopreservation (OC) consultation. Retrospective case series of all AYA (< 25years) patients with SCDs seen for OC consultation from 2011 to 2019 at a large, urban, academic fertility center. All AYA patients with an SCD seen for OC consult in the study time period were reviewed and included. Data collected included patient age, SCD type, number of patients who attempted OC, number of cycles attempted, and cycle outcomes. Twenty-two patients were included: 9 with Turner syndrome, 12 with mosaic Turner syndrome, and 1 with 47,XXX. Mean age at consult was 14.7 ± 3.5years. Fourteen patients elected for OC: 5 with Turner syndrome, 8 with mosaic Turner syndrome, and 1 47,XXX who pursued 31 OC cycles total. Of those 14 patients, 10 underwent retrieval, 9 froze oocytes, and 8 froze mature (MII) oocytes. Seven patients underwent > 1 cycle and 7 had ≥ 1 cancelation. 3/3 patients who pursued cycles after 1st cancelation never got to retrieval. Age, SCD type, and baseline FSH did not predict ability to freeze MIIs. One patient returned after OC and attempted 4 ovulation induction cycles and 2 IVF cycles; all were canceled for low response. AYA patients with SCDs have a high risk of poor response and cycle cancelation but the majority froze MIIs. Thus, setting expectations is important. A larger sample size is needed to evaluate possible clinical predictors of success.

Effect of a dual trigger on oocyte maturation in young women with decreased ovarian reserve for the purpose of elective oocyte cryopreservation.

ObjectiveThe aim of this study was to determine whether co-administration of a gonadotropin-releasing hormone (GnRH) agonist and human chorionic gonadotropin (hCG) for final oocyte maturation improved mature oocyte cryopreservation outcomes in young women with decreased ovarian reserve (DOR) compared with hCG alone.MethodsBetween January 2016 and August 2019, controlled ovarian stimulation (COS) cycles in women (aged ≤35 years, anti-Müllerian hormone [AMH] <1.2 ng/mL) who underwent elective oocyte cryopreservation for fertility preservation were retrospectively analyzed.ResultsA total of 76 COS cycles were triggered with a GnRH agonist and hCG (the dual group) or hCG alone (the hCG group). The mean age and serum AMH levels were comparable between the two groups. The duration of stimulation, total dose of follicle-stimulating hormone used, and total number of oocytes retrieved were similar. However, the number of mature oocytes retrieved and the oocyte maturation rate were significantly higher in the dual group than in the hCG group (p=0.010 and p<0.001). After controlling for confounders, the dual-trigger method remained a significant factor related to the number of mature oocytes retrieved (p=0.016).ConclusionWe showed improved mature oocyte collection and maturation rate with the dual triggering of oocyte maturation in young women with DOR. A dual trigger appears to be more beneficial than hCG alone in terms of mature oocyte cryopreservation for young women with DOR.

Oocyte cryopreservation for fertility preservation in women with ovarian endometriosis.

What is the clinical usefulness of oocyte cryopreservation for fertility preservation in women with ovarian endometriosis? Clinical characteristics were retrospectively analysed in 34 women with endometrioma before a planned ovarian cystectomy. Ovarian stimulation outcomes were compared according to laterality. A one-to-one propensity score-matched analysis was conducted to compare ovarian stimulation outcomes of the first cycle in patients with endometrioma undergoing fertility preservation with those in infertile patients without endometrioma who underwent IVF treatment. The number of oocytes cryopreserved in repeated ovarian stimulation cycles was analysed. The mean endometrioma size at diagnosis was 6.0 ± 2.5 cm. The mean age, serum anti-Mullerian hormone levels and number of oocytes cryopreserved were 30.7 ± 5.9 years, 1.85 ± 1.14 ng/ml, and 4.8 ± 3.2, respectively. The number of oocytes cryopreserved in bilateral endometrioma compared with unilateral endometrioma patients was 4.1 ± 2.9 versus 5.7 ± 3.4 (P = 0.600). In the propensity score-matched cohort (n = 22 per group), the number of oocytes retrieved was significantly lower in the patients with endometrioma undergoing fertility preservation compared with that in infertile patients without endometrioma (5.4 ± 3.8 versus 8.1 ± 4.8; P = 0.045). A total of 13 (38.2%) patients with endometrioma underwent repeated stimulation. The median (interquartile range) number of cryopreserved oocytes at the first and the second cycle were 3.0 (2.5-6.0) and 5.0 (2.5-7.5), respectively. Women with endometrioma should be counselled about oocyte cryopreservation for fertility preservation before surgery. The number of cryopreserved oocytes can be increased by repeated oocyte retrieval.

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

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). 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. 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 2038IU, 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. 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.

Oncologic oocyte cryopreservation for fertility preservation: national trends and comparison of cycle characteristics between women with and without cancer

Oncologic oocyte cryopreservation for fertility preservation: national trends and comparison of cycle characteristics between women with and without cancer

Ovarian stimulation in cancer patients: random versus conventional start

To determine if random start ovarian stimulation in cancer patients provides similar results compared to conventional stimulation starting in follicular phase. Retrospective data analysis at a single center (CEGYR). All patients undergoing oocyte cryopreservation for fertility preservation due to recent cancer diagnosis were rewied from 2012 to 2018. Patients were grouped according to random start or conventional start of the ovarian stimulation. Conventional start was defined as scheduled in early follicular phase initiation of gonadotrophins; random start was initiated at any other moment of the menstrual cycle. The analyzed variables were: number of oocytes, number of matured oocytes (metaphase II), and cycle length. 71 cycles met inclusion criteria. Oocytes were collected of 23 (33%) patients on the random start group and 48 (67%) from the conventional one. Mean age was 33.8 years old in the conventional and 33.25 years old in the random start groups. (p:0.65 IC95%, 2.04-3.23). The mean number of oocytes collected were similar 11.9 (conventional) versus 10.4 (random) (p:0.47 IC95%, 2.65-5.66) and mean number of mature oocytes vitrified was also similar (metaphase II): 9.30 (conventional) vs 7.6 (random) (p:0.34 IC95%, 1.81-5.13). The cycle duration was different, being the conventional shorter (9.7 days) than the random group (11.3 days) (p:0.0019 IC95%, 0.61-2.58). Random start stimulation cycles for cancer patients has comparable results and allows patients to start gonadotrophin stimulation irrespective of menstrual cycle phase, with no impairment of oocyte yield and only a small increase of cycle duration.

Random start versus conventional start controlled ovarian stimulation in women with cancer: comparing oocyte yield among fertility preservation cycles

To determine if random start controlled ovarian stimulation provides similar oocyte yields compared to conventional ovarian stimulation in women with cancer. Retrospective cohort study. All stimulation cycles for patients undergoing oocyte cryopreservation for fertility preservation due to recent cancer diagnoses and upcoming chemotherapy or radiation were reviewed from 2012-2018. Of the 180 oocyte cryopreservation cycles, 42 cycles (40 unique patients) met inclusion criteria. Patients were grouped into either random start or non-random cycle start. Conventional start was defined as scheduled early follicular phase (prior to cycle day six) initiation of gonadotropins. A two-sample t test was used to compare the primary outcome (number of mature oocytes cryopreserved) between the random and conventional starts. The mean number of mature oocytes cryopreserved were similar in random (n=22) and conventional start controlled ovarian stimulation cycles (n=20) (12.3 versus 10.8, p=0.58). There were no differences in cancellation rate, patient age, patient body mass index (BMI), days of stimulation, peak estradiol, or total cycle gonadotropin use. Mean BMI was 27.4. The addition of letrozole to the stimulation cycles in women with breast cancer (18 cycles) did not change the mean number of oocytes retrieved (17.5 vs 15.2, p = 0.52) or the mean number of mature oocytes cryopreserved (12.8 vs 9.7, p =0.25) compared to non-letrozole stimulation cycles. Fertility preservation is of great interest for women with cancer preparing to undergo potentially gonadotoxic cancer treatments. Random cycle start controlled ovarian stimulation reduces the time delay for initiation of cancer treatment and provides similar oocyte yields in comparison to conventional cycle start. Minimizing cancer treatment delays will expand fertility preservation options for women with cancer.Table 1Oocyte yield comparing random start versus conventional start ovarian stimulation cyclesRandom-start (n=20)Conventional Start (n=22)p-valueAge (years)28.2 (23.9-32.5)30.6 (27.1-34.2)0.37Baseline E2 (pg/mL)151 (21-280) n=16 (some data missing)66.56 (39.9-80.4) n=19 (some data missing)0.12Days of Stimulation10.5 (9.5-11.5)11.0 (10.2-11.8)0.40Peak E2 (pg/mL)1910 (1204-2617)1658 (1080-2237)0.56Total gonadotropin dose (IU)3758 (2813-4703)4643 (3833-5453)0.14Total number of oocytes aspirated (Mean and 95% CI)18.3 (13.0-23.5)14.9 (10.1-19.7)0.33Number of mature oocytes cryopreserved (Mean and 95% CI)12.3 (8.8-15.7)10.8 (6.6-15.0)0.58DiagnosisAML-2 Breast- 8 Cervix-2 Hodgkins Lymphoma-3 Neuroendocrine-1 Polycythemia-1 Sarcoma-2ALL- 1 Breast- 10 Brain- 4 Hodgkins Lymphoma-3 MDS-1 Sarcoma- 1 Open table in a new tab

Ovarian Stimulation in Patients With Cancer: Impact of Letrozole and BRCA Mutations on Fertility Preservation Cycle Outcomes.

Aromatase inhibitors (AI) have been introduced to reduce estrogen exposure in women with estrogen-sensitive cancer undergoing ovarian stimulation for oocyte/embryo cryopreservation. There have been questions regarding whether the addition of AI and the presence of BRCA mutations affect cycle outcomes. We sought to determine the impact of letrozole and BRCA mutations on fertility preservation (FP) cycle outcomes of patients undergoing ovarian stimulation with an antagonist protocol. The data were generated by the secondary analysis of a prospective database of all females diagnosed with cancer who underwent embryo or oocyte cryopreservation for FP. The final analysis included 145 patients stimulated with an antagonist protocol either using letrozole combined with recombinant follicle-stimulating hormone (rFSH; LF, n = 118) or rFSH alone (FA, n = 24). The mean number of total (15.6 [7.9] vs 10.2 [7.8]; P = .004) and mature oocytes (10.4 [5.1] vs 7.8 [3.5]; P = .044) and embryos frozen (7.7 [5.3] vs 5.3 [2.7]; P = .043) were significantly higher after LF stimulation versus FA. In the LF group, women with BRCA mutations produced significantly fewer oocytes (11.0 [8.0] vs 16.4 [7.7], P = .015) and embryos (5.1 [4.4] vs 8.2 [4.7], P = .013), compared to those who were mutation negative. After adjusting for age, body mass index, baseline FSH level, and BRCA status, LF protocol still resulted in higher number of total oocytes (95% confidence interval [CI]: 1.9 to 3.6; P = .002) mature oocyte (95% CI: 0.3 to 1.4; P = .028), and embryo yield (95% CI: 0.7 to 1.4; P = .015). In women with cancer undergoing FP, letrozole appears to enhance response to ovarian stimulation while the presence of BRCA mutations is associated with lower oocyte and embryo yield.

Oocyte Cryopreservation for Fertility Preservation in Healthy Women

Advancements in methods of fertility preservation have resulted in more options available to women seeking to postpone reproduction. Preservation of unfertilized oocytes provides women with the possibility for reproduction even after age-related declines in fertility might make conceiving a child difficult to impossible. As oocyte cryopreservation rises in popularity among women, it is crucial for nurses and other clinicians to understand the background, process, ethical issues, and risks involved to help women make informed medical decisions.

Borderline Ovarian Tumor in the Pediatric and Adolescent Population: A Case Series and Literature Review

Study ObjectiveTo determine the diagnosis, management, and outcome for children and adolescents with borderline ovarian tumor (BOT), and to provide a review of the literature on BOT in children and adolescents. DesignA retrospective cohort study of female adolescents younger than age 21 years diagnosed with BOT between January 2001 and May 2016. SettingTexas Children's Hospital, Houston, Texas. ParticipantsFourteen patients (ages 12 to 18 years) diagnosed with BOT. Main Outcome MeasuresClinical presentation, preoperative characteristics, surgical technique, cancer stage, histology, treatment, and recurrence. ResultsMedian age at diagnosis was 15.5 years, with most postmenarchal. Abdominal mass/pain were the most common presenting symptoms. Median tumor size was 16.6 cm (range, 4-32 cm). Preoperative cancer antigen 125 (CA 125) was elevated in 54% (7/13) of cases. All patients had fertility-preserving surgery, either cystectomy (CY) or unilateral salpingo-oophorectomy (USO): 5 via laparoscopy (LSC) and 9 via laparotomy. Most were stage I with 5 serous and 9 mucinous BOT histology. No one received adjuvant chemotherapy. Two patients had recurrence. One had ipsilateral recurrence 2 months after LSC CY for FIGO stage IC1 mucinous BOT. The second had contralateral recurrence 15 months after laparotomy, right USO for FIGO stage IIIC serous BOT treated with LSC CY, then a second recurrence treated with USO after oocyte cryopreservation for fertility preservation. All patients were alive at last follow-up, 1 with disease. ConclusionsBOT in children and adolescents can be treated conservatively with fertility-preserving techniques and surveillance with good outcome. The role of adjuvant therapy is not known.

Oocyte cryopreservation for fertility preservation in women with cancer.

It is necessary to clarify the fertility preservation-related points of concern that often frighten patients or physicians when it comes to deciding about oocyte cryopreservation for fertility preservation, which are often perceived as procedure limitations, are sometimes real and often theoretical and may make the prognosis worse. Letrozole added to gonadotrophins for controlled ovarian stimulation is safe when applied to hormone-sensitive cancer patients as it avoids associated high estradiol levels. This benefit is only for estrogens, but not for progesterone. Triggering ovulation with gonadotropin releasing hormone agonist bolus and adding the gonadotropin releasing hormone antagonist after oocyte retrieval help minimize its effect. A random start is currently widespread as neither results nor offspring are compromised, and it avoids waiting for menstruation and, therefore, delaying treatment. The cumulative live birth rate is conditioned by the number of available oocytes and patient's age. Assisted reproductive technologies may help cancer patients to achieve pregnancy with good obstetric outcomes and apparent oncological safety. Although counseling should be provided on an individual basis, fertility preservation in cancer patients and later pregnancy in survivors after adequate treatment and follow-up should not be discouraged.

Mature Oocyte Cryopreservation for Fertility Preservation.

In recent decades, advances in cancer treatment have led to a dramatic improvement in long term survival. This has led to an increasing focus on quality of life after surviving cancer treatment, with fertility being an important aspect. Given the known reproductive risks of cancer therapies, there has been a growing interest in the field of fertility preservation (also referred to as oncofertility). Mature oocyte cryopreservation is no longer considered experimental and has become a realistic option for reproductive aged women prior to undergoing cancer treatment. Additionally, as cryopreservation techniques improve, mature oocyte cryopreservation is increasing being marketed to healthy women without cancer wishing to delay child bearing, also termed "social egg freezing". This chapter provides a review of the current technology, use, and outcomes of mature oocyte cryopreservation. It also outlines the ethical debate surrounding social egg freezing and directions for future research in female fertility preservation.