Abstract

Abstract Study question Does ovarian follicle size influence ultimate oocyte fate and embryology outcome? Summary answer Per punctured follicle, higher oocyte yield, MII oocytes, 2PN fertilisation, and utilisable blastocyst is observed as follicle increases in size up to threshold of 15.5mm What is known already It is well known that oocyte maturity and probability of successful fertilisation is correlated to the size of follicles where oocyte originated from. However the true cutoff and ideal size at oocyte retrieval remains elusive. Furthermore, there is no conclusive evidence that embryological outcome in terms of blastocyst morphology and utilisation differs in the mid to large ovarian follicular sizes. Study design, size, duration Prospective observational study undertaken in a tertiary fertility referral centre over 10 months. 50 participants recruited and underwent conventional controlled ovarian stimulation as per unit protocol. A total of 288 follicular punctures performed in the study period. Participants/materials, setting, methods 50 oocyte retrieval (OR) procedures were performed. The size of ovarian follicles was individually measured using transvaginal ultrasound. 288 follicular punctures were performed and up to 3 oocytes per patient were collected for the study to be individually cultured to allow for tracking of oocyte and embryo outcomes. Follicular fluid and spent culture media were collected separately for subsequent metabolomics analysis. Follicular sizes were divided into 6 groups ( < =9.5, 10-12.5, 13-15.5, 16-19.5, 20-23.5, > =24). Main results and the role of chance Oocyte fate included 113 mature oocytes, 83 bipronuclear (2PN) oocytes, 7 cleavage stage embryos, and 39 good quality blastocysts suitable for utilisation in fresh or frozen transfer cycles. When compared to overall average per punctured follicle, there is an association of higher oocyte yield, proportion of MII oocytes, 2PN fertilisation, and utilisable blastocyst as follicle size increases. The threshold for a change in fate appears to be when follicle size increases beyond 15.5mm where optimal follicle size may reach plateau. Proportion of good-quality blastocysts appears to be associated with size of follicles at rates as follow- 0% (less than 10mm), 11.1% (10-12.5mm), 13.2% (13-15.5mm), 15.9% (16-19.5mm), 14.5% (20-23.5mm), and 20% (above 24mm). 23 embryos have been utilised to date, yielding a 50% positive pregnancy rate. Of these utilised embryos resulting in a positive pregnancy test, 81.8% of embryos originated from follicles above 15.5mm. Metabolomics analysis for follicular fluid and spent culture media is ongoing. Limitations, reasons for caution The observational nature of the study along with a small sample size are limitations that did not allow clinical significance to be observed. Wider implications of the findings Oocyte retrieved from follicles less than 10mm is futile. There appears to be a plateau in optimal follicle size where no real detriment is demonstrated. This is an important findings to guide stimulation, especially in cases of asynchronous growth where sacrifice in larger follicles is commonly assumed. Trial registration number Not applicable

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