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)? 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. FP is increasingly applied in assisted reproduction, but little is known about the outcome of IVF cycles with vitrified oocytes in FP patients. 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. 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. 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 in EFP (P < 0.0001), with improved outcomes when more oocytes were available for IVF. 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. 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. No external funding was used for this study. The authors have no conflicts of interest. N/A.

To compare the efficacy and safety of follitropin delta, a new human recombinant FSH with individualized dosing based on serum antimüllerian hormone (AMH) and body weight, with conventional follitropin alfa dosing for ovarian stimulation in women undergoing IVF. Randomized, multicenter, assessor-blinded, noninferiority trial (ESTHER-1). Reproductive medicine clinics. A total of 1,329 women (aged 18-40 years). Follitropin delta (AMH <15 pmol/L: 12 μg/d; AMH ≥15 pmol/L: 0.10-0.19 μg/kg/d; maximum 12 μg/d), or follitropin alfa (150 IU/d for 5 days, potential subsequent dose adjustments; maximum 450 IU/d). Ongoing pregnancy and ongoing implantation rates; noninferiority margins -8.0%. Ongoing pregnancy (30.7% vs. 31.6%; difference -0.9% [95% confidence interval (CI) -5.9% to 4.1%]), ongoing implantation (35.2% vs. 35.8%; -0.6% [95% CI -6.1% to 4.8%]), and live birth (29.8% vs. 30.7%; -0.9% [95% CI -5.8% to 4.0%]) rates were similar for individualized follitropin delta and conventional follitropin alfa. Individualized follitropin delta resulted in more women with target response (8-14 oocytes) (43.3% vs. 38.4%), fewer poor responses (fewer than four oocytes in patients with AMH <15 pmol/L) (11.8% vs. 17.9%), fewer excessive responses (≥15 or ≥20 oocytes in patients with AMH ≥15 pmol/L) (27.9% vs. 35.1% and 10.1% vs. 15.6%, respectively), and fewer measures taken to prevent ovarian hyperstimulation syndrome (2.3% vs. 4.5%), despite similar oocyte yield (10.0 ± 5.6 vs. 10.4 ± 6.5) and similar blastocyst numbers (3.3 ± 2.8 vs. 3.5 ± 3.2), and less gonadotropin use (90.0 ± 25.3 vs. 103.7 ± 33.6 μg). Optimizing ovarian response in IVF by individualized dosing according to pretreatment patient characteristics results in similar efficacy and improved safety compared with conventional ovarian stimulation. NCT01956110.

The classic, unproven dogma that ovarian endometrioma should be removed in all infertile women prior to IVF has been recently questioned. There is currently insufficient data to clarify whether the endometrioma-related damage to ovarian responsiveness precedes or follows surgery. Both endometrioma-related injury and surgery-mediated damage may be claimed to be involved and the relative importance of these two insults remains to be clarified. Convincing evidence has emerged showing that responsiveness to gonadotrophins after ovarian cystectomy is reduced. Conversely, the impact of surgery on pregnancy rates is unclear since no deleterious effect has been reported. Of relevance here is that surgery exposes women to risk related to a demanding procedure whereas risks associated with expectant management are mostly anecdotal or of doubtful clinical relevance. We recommend proceeding directly to IVF to reduce time to pregnancy, to avoid potential surgical complications and to limit patient costs. Surgery should be envisaged only in presence of large cysts (balancing the threshold to operate with the cyst location within the ovary), or to treat concomitant pain symptoms which are refractory to medical treatments, or when malignancy cannot reliably be ruled out.