Conventional ovarian stimulation and single embryo transfer for IVF/ICSI. How many oocytes do we need to maximize cumulative live birth rates after utilization of all fresh and frozen embryos?

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 (χ(2) 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.