P-419 Oocytes quality in random start protocols for fertility preservation: insights from follicular steroidogenesis.
Authors: Galati G , Serra N , Somigliana E , Ciaffaglione M , Reschini M , Sanzani E , Viganò P , Filippi F 
Published: June 2023

Abstract

Study question
Is follicular steroidogenesis impaired in women undergoing random start protocols for fertility preservation?

Summary answer
The phase of menstrual cycle at initiation of ovarian stimulation does not influence the endocrine microenvironment surrounding oocytes.

What is known already
Cryopreservation of oocytes is the gold standard for fertility preservation in women with cancer. Random start protocols have been introduced for oocytes cryopreservation in these patients to shorten the duration of ovarian stimulation. However, albeit generally reassuring, available evidence is still insufficient to rule out a sub-optimal cycle outcome of random start protocols.

Study design, size, duration
The present study was conducted to provide evidence on the validity of random start protocols by exploring the quality of ovarian steroidogenesis. The primary outcome was comparing levels of steroids in the follicular fluid between women initiating the random start protocol in the luteal phase and those initiating in the follicular phase (considered as controls since equivalent to the conventional protocols). We excluded those requiring concomitant letrozole assumption.

Participants/materials, setting, methods
Seventy-one women with cancer were prospectively recruited during a 24-month period. Thirty-three initiated in luteal phase while 38 in follicular phase. All women were stimulated with recombinant FSH and GnRH antagonists. At the time of oocytes retrieval, follicular fluids were pooled, and a sample was frozen at -80 °C. All samples were assayed concomitantly after thawing, by liquid chromatography tandem mass spectrometry. The concentration of 15 different steroid hormones was determined.

Main results and the role of chance
Baseline characteristics of the two groups were similar. No differences emerged in anamnestic data and ovarian reserve variables. Cycle outcome did not also differ, the two study groups being similar in terms of total dose of gonadotropins, duration of stimulation, number of developed follicles and number of oocytes retrieved. The median [interquartile range] number of frozen mature oocytes was 9 [5-14] and 10 [5-21] in women who initiated in the luteal and the follicular phase, respectively (p = 0.42). None of the 15 tested steroid hormones differed. Two subgroup secondary analyses were performed to rule out confounders. First, we excluded women who were on estroprogestins at the time of recruitment (leaving 31 women initiating in the follicular phase and 32 in the luteal phase). Levels of steroids in the follicular fluids were still mainly similar. We observed a significant difference only for androstenedione, levels being higher for women initiating stimulation in the follicular phase. Second, we compared women in the early (up to day 5) and late follicular phase (26 and 12 cases, respectively). Levels of steroids in the follicular fluids did not differ except for cortisone, the concentration being higher in the early follicular phase.

Limitations, reasons for caution
Our study is not randomized, inevitably exposing our results to confounders. Assessment of intraovarian steroidogenesis is an indirect evidence of oocyte quality. Multiple comparisons were done, exposing our findings to type I errors (such as, in our opinion, the differences that emerged in the secondary analyses).

Wider implications of the findings
Random start protocols have become the standard of care for fertility preservation in women with cancer in the absence of robust evidence. Our data supports the validity of random start protocols in terms of quality of ovarian response since none of the tested hormones differed.

Trial registration number
Not applicable