Double stimulation (DuoStim)

Olha Romanova
Expert of the article you are reading
chief medical officer, leading reproductologist, gynecologist, endocrinologist, MD, PhD. ; main specialty: gynecological endocrinology, treatment of infertility due to premature decline/insufficiency of ovarian function, treatment of embryo implantation disorders.

In May 2024, an important scientific event for reproductive specialists took place in Ukraine, in which the chief physician of our clinic, Olha Olehivna Romanova, took part as a speaker. The topic of the report was: how to optimize the obtaining of high-quality eggs and embryos and shorten the path to the birth of a healthy child for patients with low ovarian reserve?

In our clinic, we have been effectively using the program of double stimulation of follicle growth (DuoStim) for many years. This enables our patients to obtain a larger number of high-quality eggs in a shorter period of time, to have a sufficient number of embryos, to increase the probability of obtaining an euploid embryo (chromosomally healthy) for transfer into the uterine cavity of the expectant mother.         Double stimulation consists in the fact that during one menstrual cycle it is possible to obtain more eggs, which significantly increases the effectiveness of IVF treatment compared to the standard scheme of superovulation stimulation.

When to conduct a dual stimulation program?

  • for patients in late reproductive age (from 38)
  • with premature reduction of the ovarian reserve (when the reserve of eggs is already reduced at a young age due to a congenitally low reserve, ovarian cysts or undergone operations on the ovaries)
  • in the program of delayed motherhood (when it is important for the patient to collect the optimal number of oocytes for further fertilization in a short period of time)
  • with the low quality of the partner’s sperm, when we need to fertilize a larger number of eggs to get pregnant
  • carriers of monogenic diseases in which we need to perform PGT-M (to select an embryo that has not inherited the monogenic disease).

Double stimulation (DuoStim)

Correia et al., 2023.        

It is very important to remember how many mature oocytes need to be obtained for the birth of a child depending on the reproductive age? These data were obtained from the analysis of IVF treatment programs of patients (which took place in various treatment centers from 2014-2019) depending on the female reproductive age.  At the same time, 410,719 punctures with obtaining oocytes and 469,577 embryo transfer cycles in 311,237 women aged 18-45 were analyzed.  The data were published by a group of authors led by Correia et al. in 2023.        As can be seen from the analyzed data of 410,719 punctures of follicles performed in order to obtain oocytes up to 32 years of female reproductive age, it is necessary to fertilize 7-8 eggs on average for the birth of a child, while in the reproductive age over 42 years it is necessary to fertilize 26-34 eggs for birth children Therefore, the selection of the optimal stimulation scheme is of crucial importance for increasing the effectiveness of the IVF program.

Double stimulation (DuoStim)

Key and mandatory steps for “correct DuoStim”:

  1. First stimulation: GnRH antagonist or progestins (PPOS) with gonadotropins
  2. Ovulation trigger: GnRH agonist (required)
  3. The beginning of the second stimulation: 5-6 days after the puncture (receiving eggs)
  4. Second stimulation: GnRH antagonist or progestins (PPOS) with gonadotropins
  5. Ovulation trigger: GnRH agonist or HCG
  6. “Freeze all” strategy: at the blastocyst stage with/without PGT-A

Double stimulation (DuoStim)

This is how the follicle growth stimulation scheme looks like with DuoStim Conclusions:

  • The use of the DuoStim stimulation protocol for the treatment of patient groups with a poor prognosis for stimulation and cancer patients is increasing worldwide
  • DuoStim protocol with PGT-A (preimplantation genetic testing for aneuploidy) increases the number of oocytes/embryos obtained in a shorter period
  • The DuoStim protocol reduces the number of patients (drop-out rate) leaving the treatment program without achieving pregnancy compared to the standard stimulation protocolLPS (stimulation in the luteal phase of the menstrual cycle) in the DuoStim protocol increases the chance of obtaining a reproductively competent embryo for transfer in patients with a poor prognosis
  • Embryos obtained from FPS (stimulation in the follicular phase of the menstrual cycle) and LPS (stimulation in the luteal phase of the menstrual cycle) have, when compared, the same indicators in development, genetic and reproductive competence
  • As the final trigger of oocyte maturation in the DuoStim program, it is better to give preference to GnRHa (gonadotropin-releasing hormone agonists), as this group provides early luteolysis and facilitates the second phase of stimulation