# “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.

## Key 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.