“Reverse” Dual Stimulation Has Comparable Efficacy, but Higher Efficiency, than Two Conventional Follicular Phase Stimulations in Poor Responders Undergoing In Vitro Fertilization

TL;DR

A new method of ovarian stimulation in IVF allows immediate embryo transfer and shortens the time to pregnancy for poor responders without reducing success rates.

Contribution

Reverse dual stimulation enables fresh embryo transfer and reduces time to pregnancy compared to conventional methods in poor responders.

Findings

Reverse dual stimulation (R-DS) achieved comparable oocyte retrieval and live birth rates to conventional methods.

R-DS significantly reduced the time to pregnancy by allowing immediate fresh embryo transfer.

Progesterone levels remained low and endometrial thickness was adequate for fresh embryo transfer in R-DS.

Abstract

Background/Objectives: Dual stimulation starting in the follicular phase allows retrieval of more oocytes than single follicular-phase controlled ovarian stimulation (COS). However, dual stimulation excludes fresh embryo transfer (ET), forcing us to postpone the first ET. If dual stimulation is performed in a reverse way (“reverse”-dual stimulation, R-DS), fresh ET can be performed, potentially reducing the time to pregnancy. The aim of the present study is to investigate reproductive outcomes of R-DS compared to two consecutive COS starting in the follicular phase (2FP-COS). Methods: A retrospective study was performed on 146 poor responders matching Bologna criteria, among which 45 underwent R-DS and 101 received 2FP-COS. In the R-DS group, the first COS began 5 days after ovulation and the second 5 days after oocyte retrieval. The primary outcome was the time to pregnancy. Results: In R-DS, stimulation length, retrieved oocytes, and blastocyst formation rate were comparable in the luteal and follicular COS rounds. Circulating progesterone was always <1.0 ng/mL at ovulation trigger, and fresh ET was performed with a mean endometrial thickness of 9.27 ± 2.28 mm. Comparing R-DS and 2FP-COS, no differences were found in terms of retrieved oocytes and cumulative live birth rate; however, the R-DS group showed significantly shorter time to pregnancy (52.9 ± 11.6 vs. 103.2 ± 23.2 days, p < 0.05). Conclusions: This study suggests that R-DS is not inferior to two consecutive COS starting in the follicular phase in terms of oocytes retrieved and cumulative live birth rate. R-DS allows immediate fresh ET and can significantly shorten the time to pregnancy, a relevant issue for poor responders’ patients.

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