STUDY QUESTION What is the impact of ovarian response on cumulative live birth rates (LBR) following utilization of all fresh and frozen embryos in women undergoing their first ovarian stimulation cycle, planned to undergo single embryo transfer (SET). SUMMARY ANSWER Cumulative LBR significantly increases with the number of oocytes retrieved. WHAT IS KNOWN ALREADY Several studies have addressed the issue of the optimal number of oocytes retrieved following controlled ovarian stimulation (COS) for IVF/ICSI and demonstrated that ovarian response is independently related to LBR following IVF/ICSI. The vast majority of studies pertained only to the outcome of the fresh IVF cycle and did not evaluate the cumulative LBR following the transfer of all fresh and frozen–thawed embryos after a single ovarian stimulation, which is the most meaningful outcome for the infertile patient. STUDY DESIGN, SIZE, DURATION This study is a large cohort analysis of retrospective data from January 2009 to December 2013 in a tertiary medical centre, at the Centre for Reproductive Medicine at the University Hospital of Brussels. PARTICIPANTS/MATERIALS, SETTING, METHODS This study included 1099 eligible consecutive women 18–40 years old undergoing their first IVF cycle and planned to undergo SET in their fresh cycle. All patients were treated with a conventional starting gonadotrophin dose of 150–225 IU recombinant FSH (rFSH) in a fixed GnRH antagonist protocol. Vitrification was used as cryopreservation method. To evaluate the impact of oocyte yield on fresh LBR and on cumulative LBR after utilization of all cryopreserved embryos, patients were categorized into four groups according to the number of oocytes retrieved: 1–3 (Group A), 4–9 (Group B), 10–15 (Group C) or >15 oocytes (Group D). MAIN RESULTS AND THE ROLE OF CHANCE Regarding LBR in the fresh IVF/ICSI cycles, unadjusted results did not show any significant difference when comparing either high (>15 oocytes) versus normal (10–15 oocytes) (P = 0.65), or normal (10–15) versus suboptimal (4–9 oocytes) responders (P = 0.2). LBR in the fresh cycles were significantly higher (P < 0.05) in high, normal and suboptimal responders when compared with the low ovarian responder group (1–3 oocytes). Moderate-severe ovarian hyperstimulation syndrome occurred in 11 out of 1099 patients (1%). The cumulative LBR significantly increased with the number of oocytes retrieved (χ² test for trend P < 0.001). High responders (>15 oocytes) demonstrated a significantly higher LBR not only versus poor (0–3 oocytes) (P < 0.001) and suboptimal (4–9) responders (P < 0.001), but also versus women with normal (10–15) ovarian response (P = 0.014). Finally, although suboptimal responders had a better outcome compared with poor ovarian responders (P = 0.002), this group had a significantly lower cumulative LBR compared with normal ovarian responders (P = 0.02). Multivariate logistic regression analysis showed that the ovarian response category remained an independent predictive factor (P < 0.001) for cumulative LBR. LIMITATIONS, REASONS FOR CAUTION This is a cohort analysis based on retrospective data collection. Despite our robust methodological approach, the presence of biases related to retrospective design cannot be excluded. High responders may inherently have had a better prognosis. In addition, we cannot provide any guidance for patients undergoing either multiple embryo transfers or treated with higher gonadotrophin doses. WIDER IMPLICATIONS OF THE FINDINGS Women undergoing COS for their first IVF/ICSI cycle and SET should be informed that, although the number of oocytes retrieved does not affect LBR in the fresh cycle, the higher the oocyte yield, the higher the probability to achieve a live birth after utilization of all cryopreserved embryos. Large cohort studies are needed in order to confirm our results of cumulative LBR in different ovarian stimulation settings with higher stimulation doses. STUDY FUNDING/COMPETING INTERESTS No external funding was used for this study. No conflicts of interest are declared.

The ‘freeze-all’ strategy with the segmentation of IVF treatment, namely with the use of a GnRH antagonist protocol, GnRH agonist triggering, the elective cryopreservation of all embryos by vitrification and a frozen-thawed embryo transfer in a subsequent cycle, has become more popular. However, the approach still encounters drawbacks. In this opinion paper, a SWOT (strengths, weaknesses, opportunities and threats) analysis sheds light on the different aspects of this strategy.

Is elevated late-follicular phase progesterone (EP) associated with a deleterious impact on embryo quality (EQ) and cumulative live birth rates (LBRs)? EP was associated with a decrease in embryo utilization and cumulative LBRs. Ovarian stimulation promotes the production of progesterone (P) which adversely affects IVF pregnancy outcomes. However, evidence regarding a potential association between EP an EQ is lacking. A retrospective analysis of all GnRH antagonist down-regulated ICSI cycles followed by a fresh embryo transfer (ET) between 2010 and 2015 was performed. The sample was stratified according to the following P levels on the day of ovulation triggering: ≤0.50, 0.51-1.49 and ≥1.50 ng/ml. The primary outcomes were embryo utilization rates (number of embryos transferred or cryopreserved) and cumulative LBR, defined as the occurrence of the first live-birth after either the fresh or one of the subsequent frozen ET. Overall, 3400 cycles were included in the analysis, using multivariable regression to account for potential confounding. Female age and the number of oocytes retrieved increased significantly with increasing serum P values. Utilization rates decreased linearly as P increased for Day 3 embryos (72.3, 63.0 and 45.4%, respectively), while for Day 5 embryos only the EP group was associated with a significant decrease (48.8, 47.8 and 38.8%, respectively). EP was also associated with decreased fresh and cumulative LBRs. The main limitations of this study were its retrospective nature and the fact that it was restricted to GnRH antagonist cycles. These results raise the question whether EP may also be associated with a decrease in cumulative pregnancy outcomes by increasing embryo wastage. Further studies may evaluate the potential benefit of additional measures besides the freeze-all strategy to avoid this issue, such as lowering the stimulation dose or applying a step-down protocol. None.

The prolonged lockdown of health services providing high-complexity fertility treatments –as currently recommended by many reproductive medicine entities– is detrimental for society as a whole, and infertility patients in particular. Globally, approximately 0.3% of all infants born every year are conceived using assisted reproductive technology (ART) treatments. By contrast, the total number of COVID-19 deaths reported so far represents approximately 1.0% of the total deaths expected to occur worldwide over the first three months of the current year. It seems, therefore, that the number of infants expected to be conceived and born –but who will not be so due to the lockdown of infertility services– might be as significant as the total number of deaths attributed to the COVID-19 pandemic. We herein propose remedies that include a prognostic-stratification of more vulnerable infertility cases in order to plan a progressive restart of worldwide fertility treatments. At a time when preventing complications and limiting burdens for national health systems represent relevant issues, our viewpoint might help competent authorities and health care providers to identify patients who should be prioritized for the continuation of fertility care in a safe environment.