There has been a sharp increase in the demand for fertility preservation. This review summarizes the indications and current options and describes new techniques and strategies, including those for women with newly diagnosed malignant disease.

https://www.nejm.org/doi/suppl/10.1056/NEJMra1614676/suppl_file/nejmra1614676_appendix.pdf

Fertility Preservation in Women

Oocyte vitrification as an efficient option for elective fertility preservation

Aside from inheriting half of the genome of each of our parents, we are born with a small number of novel mutations that occurred during gametogenesis and postzygotically. Recent genome and exome sequencing studies of parent–offspring trios have provided the first insights into the number and distribution of these de novo mutations in health and disease, pointing to risk factors that increase their number in the offspring. De novo mutations have been shown to be a major cause of severe early-onset genetic disorders such as intellectual disability, autism spectrum disorder, and other developmental diseases. In fact, the occurrence of novel mutations in each generation explains why these reproductively lethal disorders continue to occur in our population. Recent studies have also shown that de novo mutations are predominantly of paternal origin and that their number increases with advanced paternal age. Here, we review the recent literature on de novo mutations, covering their detection, biological characterization, and medical impact.

https://link.springer.com/content/pdf/10.1186%2Fs13059-016-1110-1.pdf

New insights into the generation and role of de novo mutations in health and disease.

Introduction Since the first live birth from oocyte cryopreservation three decades ago, oocyte cryopreservation has become an important component of ART. Cryopreservation techniques have evolved, leading to higher success rates and the introduction of oocyte cryopreservation into IVF clinics worldwide. Concurrently, there has been an increase in patient demand, especially for so-called 'social egg freezing' that allows women to preserve their fertility in anticipation of age-related fertility decline. This review addresses a need to evaluate the current status of oocyte cryopreservation. It explores current techniques and success rates, clinical applications, the rise of elective oocyte cryopreservation, and future implications. Methods A search was performed using Web of Science and PubMed databases for publications between January 1980 and December 2015. Keywords used included 'egg freezing', 'oocyte freezing', 'oocyte cryopreservation', 'oocyte vitrification', and 'fertility preservation'. Results The success rate of oocyte cryopreservation has risen, and the increasing use of vitrification offers has improved outcomes, with IVF pregnancy rates now similar to those achieved with fresh oocytes. There are conflicting opinions about the comparative success rates of open and closed vitrification. Patients are accessing and receiving oocyte cryopreservation for a wide range of indications, and there has been a marked increase in patient numbers and oocyte cryopreservation cycles. Oocyte cryopreservation for circumventing age-related infertility is becoming more widely accepted. Conclusion Oocyte cryopreservation is an established component of ART, with vitrification now being the cryopreservation technique of choice. Increasing numbers of women undergo oocyte cryopreservation for both medical and social reasons. It is important to continue auditing outcomes and reporting long-term follow-up of children born from frozen-thawed oocytes.

/pdf/oocyte-cryopreservation-where-are-we-now-3wfoo2f0m2.pdf

Oocyte cryopreservation: where are we now?

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 0.05). Fewer EFP cycles finished in embryo transfer (50.2% vs. 72.5%) (P 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. TRIAL REGISTRATION NUMBER N/A.

/pdf/elective-and-onco-fertility-preservation-factors-related-to-4l3jq7ra29.pdf

Elective and Onco-fertility preservation: factors related to IVF outcomes.

Effect of oocyte vitrification on embryo quality: time-lapse analysis and morphokinetic evaluation.

Analysis of the morphological dynamics of blastocysts after vitrification/warming: defining new predictive variables of implantation.

This study aimed to determine whether the new formulation of vitrification solutions containing a combination of hydroxypropyl cellulose (HPC) and trehalose does not affect outcomes in comparison with using conventional solutions made of serum substitute supplement (SSS) and sucrose. Ovum donation cycles were retrospectively compared regarding the solution used for vitrification and warming of human oocytes. The analysis included 218 cycles (N = 2532 oocytes) in the study group (HPC + trehalose) and 214 cycles (N = 2353 oocytes) in the control group (SSS + sucrose). No statistical differences were found in ovarian stimulation parameters and baseline characteristics of donors and recipients. The survival rate was 91.3 % (95 % confidence interval (CI) = 89.8–92.9) in the HPC + trehalose group vs. 92.1 % (95 % CI = 90.4–93.7) in the SSS + sucrose group (NS). The implantation rate (42.8 %, 95 % CI = 37.7–47.9 vs. 41.2 %, 95 % CI = 36.0–46.4), clinical pregnancy rate (CPR) per transfer (60.7 %, 95 % CI = 53.9–67.5 vs. 56.4 %, 95 % CI = 49.3–63.5), and ongoing pregnancy rate (OPR) per transfer (48.5 %, 95 % CI = 41.5–55.5 vs. 46.3 %, 95 % CI = 39.2–53.4) were similar for patients who received either HPC + trehalose-vitrified oocytes or SSS + sucrose-vitrified oocytes. Statistical differences were found when analyzing blastocyst rate both per injected oocyte (30.2 %, 95 % CI = 28.3–32.1 vs. 24.1 %, 95 % CI = 22.3–25.9) and per fertilized oocyte (40.8 %, 95 %CI = 38.5–43.1 vs. 33.2 %, 95 % CI = 30.8–35.5) (P < 0.0001). Delivery rate was comparable between groups (37.2 %, 95 % CI = 30.8–46.6 vs. 36.9 %, 95 % CI = 30.4–43.4; NS). Our data demonstrate that HPC and trehalose are suitable and safe substitutes for serum and sucrose. Therefore, the new commercial media can be used efficiently in the vitrification of human oocytes avoiding viral and endotoxin contamination risk.

/pdf/a-combination-of-hydroxypropyl-cellulose-and-trehalose-as-29wrf0pbqz.pdf

A combination of hydroxypropyl cellulose and trehalose as supplementation for vitrification of human oocytes: a retrospective cohort study.

Research question How does the number of oocytes used affect the cumulative live birth rate (CLBR) in endometriosis patients who had their oocytes vitrified for fertility preservation? Design Retrospective observational study including data from 485 women with endometriosis who underwent fertility preservation from January 2007 to July 2018. Survival curves and Kaplan–Meier plots were used to analyse the CLBR according to the number of vitrified oocytes used. Endometriosis curves were compared with plots developed using elective fertility preservation (EFP) patients as control group. Log-rank, Breslow and Tarone–Ware tests were used to compare the survival curves. Results The CLBR increased as the number of oocytes used per patient rose, reaching 89.5% (95% confidence interval [CI] 80.0–99.1%) using 22 oocytes. Higher outcomes were observed in young women (≤35 years old versus >35 years old). In the younger group, the CLBR was 95.4% (95% CI 87.2–103.6%) using approximately 20 oocytes versus 79.6% (95% CI 58.1–101.1%) in older women (log-rank [Mantel–Cox] P = 0.002). The mean age was higher in EFP patients (37.2 ± 4.9 versus 35.7 ± 3.7; P  Conclusion The probability of live birth increases as the number of oocytes used increases in patients with endometriosis, but better outcomes were observed among young women. The information provided here may be of interest to both patients and treating physicians for counselling purposes.

A. Coello

Papers

Oocyte vitrification as an efficient option for elective fertility preservation

Effect of oocyte vitrification on embryo quality: time-lapse analysis and morphokinetic evaluation.

Analysis of the morphological dynamics of blastocysts after vitrification/warming: defining new predictive variables of implantation.

A combination of hydroxypropyl cellulose and trehalose as supplementation for vitrification of human oocytes: a retrospective cohort study.

Number needed to freeze: cumulative live birth rate after fertility preservation in women with endometriosis