O-134 Pretreatment with luteal estradiol for programming antagonist cycles compared to no pretreatment in advanced age women treated with corifollitropin alfa: a randomized controlled trial
Authors: Cedrin - Durnerin I , Massin N , Chevallier N , Carton I , Goro S , Jung C , Guivarc’h-Leveque A 
Published: June 2023

Abstract

Study question
Does luteal estradiol pretreatment improve the number of oocytes retrieved in women aged 38 to 43 years treated in antagonist protocol with corifollitropin alfa?

Summary answer
Programming antagonist cycles with luteal estradiol did not increase the number of retrieved oocytes in advanced age women, however it was effective for programming.

What is known already
Previous studies showed that programming IVF cycles with estradiol pretreatment is a valuable tool for the organization of IVF centers and patients. However, variable effects of estradiol pretreatment were observed on the number of retrieved oocytes: no difference in normal responders, improved yield in oocyte donors and conflicting results in poor responders but no improvement in those fulfilling the bologna criteria. In advanced age women, recruitable follicles tends to decrease in number and to be more heterogeneous in size but it remains unclear if estradiol pretreatment could yield more oocytes through its negative feed-back effect on FSH intercycle rise.

Study design, size, duration
This non-blinded randomized controlled trial was conducted between 2016 and 2022. Participants were 324 women aged 38 to 43 years who requested IVF treatment. The primary endpoint was the comparison of the total number of retrieved oocytes between pretreated (P) and no pretreated (NP) patients. Secondary endpoints were duration and total dosage of recombinant FSH, cancellation rate, total number of metaphase II oocytes and obtained embryos, fresh transfer live birth rate (LBR) and cumulative LBR.

Participants/materials, setting, methods
This multicentric study (6 centers) enrolled women with regular cycles, weight &gt;50 kg and BMI &lt;32, IVF rank 1-2. According to computerized randomization, micronized estradiol 2mg twice a day was started on day (D) 20-24 continued until Wednesday beyond the onset of menses followed by administration of corifollitropin alfa on Friday i.e. stimulation (S)1 or from D1-3 of a natural cycle in unpretreated patients. GnRH antagonist was started at S6 and additional rFSH at S8.

Main results and the role of chance
Basal characteristics were similar in estradiol P (n = 147; number (mean [SD]) of treatment days 9.8[2.6]) and NP patients (n = 144), both displaying however a wide range of AMH levels (0.3 to 11.6 ng/ml) for advanced age patients. The cancellation rate showed a trend to be lower in P group (11 vs 19 %, p = 0.11). The mean number of retrieved oocytes was lower in P compared to NP patients (8.4[6.1] vs 9.1[6], respectively). The treatment difference was -0.7[-2.1 ;0.8] p = 0.03 one tailed test . No significant differences were observed in the number of MII oocytes (7[5.5] vs 7.3[5.2], p = 0.72) and the number of obtained embryos (5[4.6] vs 5.2[4.2], p = 0.60) between the two groups. Oocytes retrieval was more often on working days in P patients (91.9 vs 74.2 %, p &lt; 0.001). However, the duration of stimulation was significantly longer (11.7[1.7] vs 10.8[1.8] days, p &lt; 0.001) and the extra rFSH dosage in addition to corifollitropin alfa was significantly higher (1040[548] vs 778[504] IU, p &lt; 0.001) in P than NP patients. The LBR after fresh transfer in P patients (16.2%[16/99]) was not significantly different from that in NP patients (18.5%[17/92]), p = 0.82, nor the cumulative LBR per patients 19.1 % vs 26.4 %, p = 0.16 respectively.

Limitations, reasons for caution
Our stimulated women older than 38 years obtained a wide range of collected oocytes (0 to 29) suggesting very different stages of ovarian aging in both groups. Estradiol pretreatment is more susceptible to increase oocyte yield at the stage of ovarian aging characterized by asynchrony of a reduced follicular cohort

Wider implications of the findings
Programming antagonist cycles with luteal estradiol pretreatment is effective in advanced age women to better schedule oocyte retrievals on working days. However, the potential benefit on the number of collected oocytes remains to be demonstrated in a more selected population displaying the characteristics of Poseïdon groups 3 and 4.

Trial registration number
ClinicalTrials.gov NCT02884245