In recent years, various advances have led to improved results in fertility treatments. One of the most significant advances in cases of low ovarian reserve or advanced maternal age is double ovarian stimulation, also known as DuoStim.
This protocol involves performing two ovarian stimulations within the same menstrual cycle: one in the follicular phase and a second in the luteal phase, with the aim of obtaining a greater number of mature oocytes in less time.
Origin of the DuoStim protocol: the scientific basis
The possibility of stimulating the ovary at different times during the cycle arose from experience in urgent fertility preservation in cancer patients. It was demonstrated that stimulation can be performed without waiting for the start of the menstrual cycle.
In 2013, Drs Xu and Li published the first case of a second stimulation after having performed one in the follicular phase. A year later, Dr Kuang and his team presented the Shanghai Protocol, based on studies that showed that several cohorts of growing follicles develop in the same cycle. Although not all follicles complete the cycle until ovulation, they can be stimulated to obtain mature oocytes.
How is the DuoStim protocol applied?
The standard procedure is as follows:
- First ovarian stimulation during the follicular phase.
- Puncture and collection of oocytes.
- Start of the second ovarian stimulation after the puncture (between 3 and 5 days later).
- Second collection of oocytes during the luteal phase.
During this interval, the oocytes from the first phase are inseminated and cultured until day 5, which allows the number and quality of embryos obtained to be assessed. This information helps to decide whether a second stimulation is appropriate, adapting the protocol to each patient on an individual basis.
Physiological basis
DuoStim is based on the theory of multiple follicular waves, which suggests that the ovaries develop several groups of follicles during the same cycle. Taking advantage of both the follicular and luteal phases allows for an increase in the number of oocytes obtained without negatively affecting their quality.
Currently, most centres begin the second stimulation around day 5 after the first puncture, as described by Ubaldi’s group.
Advantages over conventional stimulation
Conventional stimulation may be insufficient for some patients, especially those with low ovarian reserve or advanced maternal age. DuoStim offers:
- A greater number of oocytes in a single menstrual cycle.
- Reduced treatment times.
- The possibility of adapting the strategy in real time.
- More options for obtaining genetically normal embryos.
The strategy is particularly useful when preimplantation genetic testing (PGT-A) is required, as having more embryos increases the chance of finding a euploid one.
The DuoStim protocol has established itself as an effective strategy for improving oocyte retrieval rates in patients with a poorer prognosis. Its application makes it possible to shorten treatment times, personalise treatments and increase the efficiency of the reproductive process.
In future articles, we will explore the emotional benefits, clinical indications and comparative results of this protocol compared to other strategies.
- Baerwald AR, Adams GP, Pierson RA. Ovarian antral folliculogenesis during the human menstrual cycle: a review. Hum Reprod Update. 2012;18(1):73–91.
- Kuang Y, Chen Q, Hong Q, et al. Double stimulations during the follicular and luteal phases of poor responders in IVF/ICSI programmes (Shanghai protocol). Reprod Biomed Online. 2014;29(6):684–691.
- Xu B, Li Z. Second stimulation after follicular phase stimulation: first report. Case Report. 2013.
- Ubaldi FM, et al. Surfing follicular waves in ovarian stimulation: is there a role for LH in DuoStim protocols? Reprod Biol Endocrinol. 2025;23(Suppl 1):28.
