Abstract and Introduction
Study Question: Is the indication for fertility preservation (FP) related to success in IVF cycles after elective-FP (EFP) for age-related fertility decline and FP before cancer treatment (Onco-FP)?
Summary Answer: Although success rates were lower in cancer patients, there was no statistically significant association between malignant disease and reproductive outcome after correction for age and controlled-ovarian stimulation (COS) regime.
What is Known Already: FP is increasingly applied in assisted reproduction, but little is known about the outcome of IVF cycles with vitrified oocytes in FP patients.
Study Design, Size, Duration: Retrospective, observational multicenter study of vitrification cycles for FP and of the warming cycles of women who returned to attempt pregnancy from January 2007 to May 2018.
Participants/Materials, Setting, Methods: In all, 6362 women (EFP = 5289 patients; 7044 cycles + Onco-FP = 1073 patients; 1172 cycles) had their oocytes vitrified for FP. A logistic regression analysis was performed to examine the impact of indication for FP corrected for age at vitrification. The protocol used for COS was also included as a possible confounder. The main outcome measures were oocyte survival and live birth. A detailed description of the baseline and clinical data is provided, with comparisons between EFP and Onco-FP. The cumulative live birth rate (CLBR) per utilized oocyte according to age at vitrification was analyzed in those patients returning to use their oocytes.
Main Results and Role of Chance: Age at vitrification was significantly older in EFP patients (37.2 ± 4.9 vs. 32.3 ± 3.5 year; P < 0.0001). Fewer oocytes were retrieved and vitrified per cycle in EFP (9.6 ± 8.4 vs. 11.4 ± 3.5 and 7.3 ± 11.3 vs. 8.7 ± 2.1, respectively; P < 0.05), but numbers became comparable when analyzed per patient (12.8 ± 7.4 vs. 12.5 ± 3.2 and 9.8 ± 6.4 vs. 9.5 ± 2.6). Storage time was shorter in EFP (2.1 ± 1.6 vs. 4.1 ± 0.9 years; P < 0.0001). In all, 641 (12.1%) EFP and 80 (7.4%) Onco-FP patients returned to attempt pregnancy (P < 0.05). Overall oocyte survival was comparable (83.9% vs. 81.8%; NS), but lower for onco-FP patients among younger (≤35 year) subjects (81.2% vs. 91.4%; P > 0.05). Fewer EFP cycles finished in embryo transfer (50.2% vs. 72.5%) (P < 0.05). The implantation rate was 42.6% and 32.5% in EFP versus Onco-FP (P < 0.05). Ongoing pregnancy (57.7% vs. 35.7%) and live birth rates (68.8% vs. 41.1%) were higher in EFP patients aged ≤35 than the Onco-FP matching age patients (P < 0.05). The reason for FP per se had no effect on oocyte survival (OR = 1.484 [95%CI = 0.876–2.252]; P = 0.202) or the CLBR (OR = 1.275 [95%CI = 0.711–2.284]; P = 0.414). Conversely, age (<36 vs. ≥36 y) impacted oocyte survival (adj.OR = 1.922 [95%CI = 1.274–2.900]; P = 0.025) and the CLBR (adj.OR= 3.106 [95%CI = 2.039–4.733]; P < 0.0001). The Kaplan–Meier analysis showed a significantly higher cumulative probability of live birth in patients <36 versus >36 in EFP (P < 0.0001), with improved outcomes when more oocytes were available for IVF.
Limitations, Reasons for Caution: Statistical power to compare IVF outcomes is limited by the few women who came to use their oocytes in the Onco-FP group. The patients' ages and the COS protocols used were significantly different between the EFP and ONCO-PP groups.
Wider Implications of the Findings: Although the implantation rate was significantly lower in the Onco-FP patients the impact of cancer disease per se was not proven'. EFP patients should be counseled according to their age and number of available oocytes.
Study Funding/Competing Interest(s): No external funding was used for this study. The authors have no conflicts of interest.
Fertility preservation (FP) has become a new assisted reproduction area that provides women the possibility of childbearing using their own gametes after age-related decline in fertility or after antineoplastic therapies for cancer (Rienzi et al., 2017; Martinez, 2017a; Niederberger et al., 2018). Oocyte vitrification as a FP method is undoubtedly one of the greatest advances made in assisted reproduction in recent years. Lately, a growing number of women seeking to postpone motherhood have chosen to preserve their fertility by oocyte vitrification (Cobo et al., 2016). Furthermore, cancer survivors are ideal candidates for FP owing to the occurrence of ovarian failure brought on by gonadotoxic treatments. Thus, onco-fertility is another emerging branch in assisted reproduction. Of all the different options available for cancer patients, vitrification of MII oocytes is the preferred option, at least for post-pubertal patients (Martinez, 2017a,b).
Although the demand for this strategy in both elective and oncological settings has increased in recent years, very little evidence about the outcomes of IVF cycles in the FP population (i.e. cycles conducted after oocyte vitrification to safeguard fertility) is available in the literature. A study published by our group provided data on the outcomes achieved by 137 women who chose elective-FP and returned to attempt pregnancy (EFP; Cobo et al., 2016). In that study, age at retrieval/vitrification and number of oocytes were identified as factors strongly related to success. Another simultaneously published study, which included 128 autologous IVF cycles with vitrified oocytes of which 32 came from EFP patients, reached similar conclusions (Doyle et al., 2016). Evidence is even scarcer for those cancer patients who have returned to use their stored oocytes once they have overcome all the pitfalls related to their disease. A couple of case reports inform about the birth of three babies after using cryopreserved oocytes by slow freezing before cancer treatment in two patients (Yang et al., 2007; Porcu et al., 2008). Reports about using vitrified oocytes in cancer patients are also scarce. One study has reported the birth of twins after the combined use of ovarian tissue cryopreservation and vitrified oocytes harvested after tissue grafting (Sanchez-Serrano et al., 2010). Another publication by our group reports the birth of a healthy baby boy in a patient diagnosed with non-Hodgkin's lymphoma (Garcia-Velasco et al., 2013). Additionally, few other case reports have been published that report the live births achieved by FP patients affected by different cancer types (Kim et al., 2011; Alvarez et al., 2014; da Motta et al., 2014).
Due to the increasing interest in FP, it is crucial for reproductive medicine providers to be aware of the success rates and limiting factors of oocyte vitrification in order to provide patients with proper counseling. This study comprises the largest series published to date, includes both EFP and Onco-FP patients, and aims to analyze the current scope of the approach in the two different populations. Thus, our study focuses on the impact of the indication for FP on the results by comparing IVF data, oocyte survival, clinical results and live birth rates. The information provided herein can extend knowledge about the current state of oocyte vitrification as a means to safeguard fertility.
Hum Reprod. 2018;33(12):2222-2231. © 2018 Oxford University Press