Comparison In Vitro Fertilization Outcomes between DouStim and Minimal Stimulation Protocols in Poor Ovarian Responders: A Randomized Clinical Trial

Document Type : Original Article

Authors

1 Preventive Gynecology Research Center, Taleghani Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran

2 Preventive Gynecology Research Center, Taleghani Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Abstract

Background: Various protocols have been approved to improve the response rate leading to successful fertilization
in poor ovarian responders (PORs). The application of double ovarian stimulation (DuoStim) in the follicular and
luteal phases of the same ovarian cycle has been shown as an intriguing option to achieve more oocyte retrievals in
the shortest time. The aim of the current study, is to compare the outcomes of different protocols, minimal stimulation
(MS) and Duostim.
Materials and Methods: This randomized clinical trial was performed on 42 in vitro fertilization (IVF) candidates
with POR diagnosis. Patients were classified into two equal groups and treated with the DuoStim protocol and MS
protocol. The IVF outcomes, including retrieved follicles, oocytes, metaphase II (MII) oocytes and embryos, were
compared between these groups.
Results: The patients’ characteristics including age, anti-mullerian hormone (AMH), follicle-stimulating hormone
(FSH), luteinizing hormone (LH), and antral follicle count (AFC) were collected and compared. It showed there was
no significant difference between the two groups' baseline characteristics (P>0.05). We observed that the DuoStim
protocol resulted in a significantly higher score in comparison with the MS protocols, including the number of follicles
(6.23 ± 2.93 vs. 1.77 ± 1.66, P<0.001), retrieved oocytes (3.86 ± 2.57 vs. 1.68 ± 1.58, P=0.002), MII oocytes (3.36 ±
2.42 vs. 1.27 ± 1.27, P=0.001) and obtained embryos (2.04 ± 1.64 vs. 0.77 ± 0.86, P=0.003).
Conclusion: The DuoStim protocol is a favourable and time saving plan that is associated with more oocytes in a single
stimulation cycle. The DuoStim protocol significantly can result in more frequent MII oocytes and embryos. We figured
that the higher number of oocytes and embryos might have led to a higher rate of pregnancy (registration number:
IRCT20200804048303N1).

Keywords

Main Subjects


  1. Muasher SJ, Garcia JE, Rosenwaks Z. The combination of follicle-stimulating hormone and human menopausal gonadotropin for the induction of multiple follicular maturation for in vitro fertilization. Fertil Steril. 1985; 44(1): 62-69.
  2. Jones HW Jr, Acosta AA, Andrews MC, Garcia JE, Jones GS, May­er J, et al. Three years of in vitro fertilization at Norfolk. Fertil Steril. 1984; 42(6): 826-834.
  3. Stimpfel M, Vrtacnik-Bokal E, Pozlep B, Virant-Klun I. Comparison of GnRH agonist, GnRH antagonist, and GnRH antagonist mild protocol of controlled ovarian hyperstimulation in good prognosis patients. Int J Endocrinol. 2015; 2015: 385049.
  4. van Loenen AC, Huirne JA, Schats R, Hompes PG, Lambalk CB. GnRH agonists, antagonists, and assisted conception. Semin Re­prod Med. 2002; 20(4): 349-364.
  5. Jain T, Gupta RS. Trends in the use of intracytoplasmic sperm in­jection in the United States. N Engl J Med. 2007; 357(3): 251-257.
  6. Kulkarni AD, Jamieson DJ, Jones HW Jr, Kissin DM, Gallo MF, Ma­caluso M, et al. Fertility treatments and multiple births in the United States. N Engl J Med. 2013; 369(23): 2218-2225.
  7. Mansour R, Ishihara O, Adamson GD, Dyer S, de Mouzon J, Nygren KG, et al. International committee for monitoring assisted reproductive technologies world report: assisted reproductive tech­nology 2006. Hum Reprod. 2014; 29(7): 1536-1551.
  8. Simon T, Oehninger S, Toner J, Jones D, Muasher S. High doses of gonadotropins have no detrimental effect on in vitro fertilization out­come in normal responders. Fertil Steril. 1995; 63(6): 1333-1336.
  9. Qublan HS, Amarin Z, Tahat YA, Smadi AZ, Kilani M. Ovarian cyst formation following GnRH agonist administration in IVF cycles: in­cidence and impact. Hum Reprod. 2006; 21(3): 640-644.
  10. Collins J. Mild stimulation for in vitro fertilization: making progress downward. Hum Reprod Update. 2009; 15(1): 1-3.
  11. Muasher SJ, Abdallah RT, Hubayter ZR. Optimal stimulation proto­cols for in vitro fertilization. Fertil Steril. 2006; 86(2): 267-273.
  12. Zhang J, Silber S. Response: low-intensity IVF: real progress? Re­prod Biomed Online. 2012; 24(2): 254.
  13. Zarek SM, Muasher SJ. Mild/minimal stimulation for in vitro ferti­lization: an old idea that needs to be revisited. Fertil Steril. 2011; 95(8): 2449-2455.
  14. Kuang Y, Chen Q, Hong Q, Lyu Q, Ai A, Fu Y, 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.
  15. Zhang J. Luteal phase ovarian stimulation following oocyte retriev­al: is it helpful for poor responders? Reprod Biol Endocrinol. 2015; 13: 76.
  16. Ubaldi FM, Capalbo A, Vaiarelli A, Cimadomo D, Colamaria S, Alviggi C, et al. Follicular versus luteal phase ovarian stimulation during the same menstrual cycle (DuoStim) in a reduced ovarian reserve population results in a similar euploid blastocyst formation rate: new insight in ovarian reserve exploitation. Fertil Steril. 2016; 105(6): 1488-1495. e1.
  17. Lazer T, Dar S, Shlush E, Al Kudmani BS, Quach K, Sojecki A, et al. Comparison of IVF outcomes between minimal stimulation and high-dose stimulation for patients with poor ovarian reserve. Int J Reprod Med. 2014; 2014: 581451.
  18. Luo Y, Sun L, Dong M, Zhang X, Huang L, Zhu X, et al. The best execution of the DuoStim strategy (double stimulation in the follicular and luteal phase of the same ovarian cycle) in patients who are poor ovarian responders. Reprod Biol Endocrinol. 2020; 18(1): 102.
  19. Glujovsky D, Pesce R, Miguens M, Sueldo CE, Lattes K, Ciapponi A. How effective are the non-conventional ovarian stimulation pro­tocols in ART? A systematic review and meta-analysis. J Assist Re­prod Genet. 2020; 37(12): 2913-2928.
  20. Patil E, Jensen JT. Update on permanent contraception options for women. Curr Opin Obstet Gynecol. 2015; 27(6): 465-470.
  21. McLaren JF, Molinaro TA, Croly SL, Coutifaris C, Dokras A. Total failed fertilization in IVF: current etiologies and predictors. Fertil Steril. 2008; 90: S338-S3399.
  22. Vaiarelli A, Cimadomo D, Trabucco E, Vallefuoco R, Buffo L, Dusi L, et al. Double stimulation in the same ovarian cycle (DuoStim) to maximize the number of oocytes retrieved from poor prognosis patients: a multicenter experience and SWOT analysis. Front En­docrinol (Lausanne). 2018; 9: 317.
  23. Cecchino G, Cerrillo M, Cruz M, Garcia-Velasco J. Retrospective analysis of DuoStim cycles shows similar overall performance and oocyte quality between follicular and luteal phase stimulation. Hum Reprod. 2018; 36 Suppl 1: P-705.
  24. Vaiarelli A, Cimadomo D, Ubaldi N, Rienzi L, Ubaldi FM. What is new in the management of poor ovarian response in IVF? Curr Opin Obstet Gynecol. 2018; 30(3): 155-162.
  25. Kamath MS, Maheshwari A, Bhattacharya S, Lor KY, Gibreel A. Oral medications including clomiphene citrate or aromatase inhibi­tors with gonadotropins for controlled ovarian stimulation in wom­en undergoing in vitro fertilisation. Cochrane Database Syst Rev. 2017; 11(11): CD008528.
  26. Zhang X, JI J, Liu Y. The applications of double stimulations and mild ovarian stimulation with GnRH-antagonist in patients with decreased ovarian reserve. Acta Universitatis Medicinalis Anhui. 2015; (6): 1489-1493.
  27. Liu C, Jiang H, Zhang W, Yin H. Double ovarian stimulation during the follicular and luteal phase in women ≥38 years: a retrospective case-control study. Reprod Biomed Online. 2017; 35(6): 678-684.