Effect of Reducing the Oxygen Concentration From 5% to 2% on ICSI Outcome

IVF Clinical Trial

Official title:

Effect of Reducing the Oxygen Concentration From 5% to 2% on Intracytoplasmic Sperm Injection (ICSI) Outcome

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05924048
• Other study ID #: O2 level in human embryo
• Status: Recruiting
• Phase: N/A
• Start date: January 1, 2023
• Est. completion date: March 25, 2024

Study information

• Verified date: June 2023
• Source: International Islamic Center for Population Studies and Research
• Contact: Ahmed El Sayed Sabry
• Phone: 01098609545
• Email: ahmedsabry7787[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

To assess the effect of reducing the oxygen concentration from 5% to 2% on Intracytoplasmic sperm injection (ICSI) outcome.

Description:

Oxygen level plays a critical role in reducing the high level of detrimental reactive oxygen species within cells, influences embryonic gene expression, helps with embryo metabolism of glucose, and enhances embryo development from 2PN to the blastocyst stage, the oxygen concentration in the incubator is an important determinant of the in vitro environment that an embryo encounters. The preimplantation embryo consumes oxygen at a relatively constant level from the one-cell through the morula stage, while at the blastocyst stage the consumption is considerably increased. Oxygen plays a role in energy production, but in too high concentrations it may have a toxic effect by the formation of reactive oxygen species. While in vivo oxygen levels range from 1.5 to 8.7% in the fallopian tubes and uterus of several species, in most laboratories in vitro culture of human embryos was traditionally performed under atmospheric oxygen concentrations (~20%) . In mammals, the oxygen (O2) tension in the uterus is lower (2%) than the oviduct (5-7%). This fits with a shift in the metabolic strategy of the embryo after compaction and may have implications for EC in clinical IVF. Indeed, in a recent study utilizing discarded human embryos, blastulation rates were superior when cultured in 2% compared to 5% after day day 3. However, it is exceedingly difficult to control for the myriad factors impacting blastulation when employing discarded material . The technologies available in the early days of IVF, and most likely also for financial reasons, led to the widespread implementation of incubators that used atmospheric air (i.e. 20% oxygen) . Around the turn of the last century, more advanced incubators capable of creating an environment of 5% oxygen, which better resembles the natural

environment for oocytes and embryos, were developed. Currently, in around 60% of the IVF cycles performed worldwide, the embryos are cultured under 5% oxygen . Kaser et al. add to the long history of experimental data evaluating different oxygen levels in embryo culture. They evaluated the impact of a sequential oxygen tension system (5% oxygen from day 1 to day 3; 2% oxygen from day 3 to day 5) in extended culture . The effect of oxygen level during embryo culture on pregnancy and live birth rates is less straightforward. Although most studies found an improvement in embryo quality when culturing embryos under 5% oxygen . This discrepancy is partly explained by lack of power due to small sample sizes in some studies. When data are pooled in meta-analyses, the overall effect favours culture under 5% oxygen . Another explanation for the inconsistent results among the studies could be due to the differences in duration of exposure, until cleavage or blastocyst stage. When data in the meta-analyses were stratified for duration of culture, there was no effect of oxygen on pregnancy or live birth rates after 2-3 days of culture. After culture to the blastocyst stage, however, culture under 5% oxygen resulted in improved ongoing pregnancy. In the previous studies reported that culture under 5% O2 results in significantly more human surplus embryos reaching the blastocyst stage, as well as a higher proportion of blastocysts consisting of a normal number of cells.

in the human, indirect evidence exists that a low O2 tension of 5% appears to enhance the blastulation rate of surplus embryos .

A reduction in oxygen tension from atmospheric to more physiologic levels is beneficial for the mammalian blastocyst, in terms of a higher cell number and decreased apoptosis, less DNA fragmentation and less oxidative stress. During this highly metabolically active period of growth of the embryo and differentiation into trophectoderm (TE) and inner cell mass (ICM), this decrease in oxygen may protect against oxidative stress .

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 196
• Est. completion date: March 25, 2024
• Est. primary completion date: January 27, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 20 Years to 35 Years

Eligibility

Inclusion Criteria:

• Female age 20-35 years. Oocytes with normal morphology.

Exclusion Criteria:

• Embryo number less than 5. Male factor.

Related Conditions & MeSH terms

• IVF

Intervention

Other:
• Reducing the Oxygen Concentration From 5% to 2%
Effect of Reducing the Oxygen Concentration From 5% to 2% in arm 1.

Locations

Country	Name	City	State
Egypt	International Islamic Center	Cairo

Sponsors (1)

Lead Sponsor	Collaborator
International Islamic Center for Population Studies and Research

Country where clinical trial is conducted

Egypt, 

References & Publications (11)

Bahceci M, Ciray HN, Karagenc L, Ulug U, Bener F. Effect of oxygen concentration during the incubation of embryos of women undergoing ICSI and embryo transfer: a prospective randomized study. Reprod Biomed Online. 2005 Oct;11(4):438-43. doi: 10.1016/s1472 — View Citation

Bontekoe S, Mantikou E, van Wely M, Seshadri S, Repping S, Mastenbroek S. Low oxygen concentrations for embryo culture in assisted reproductive technologies. Cochrane Database Syst Rev. 2012 Jul 11;(7):CD008950. doi: 10.1002/14651858.CD008950.pub2. — View Citation

Christianson MS, Zhao Y, Shoham G, Granot I, Safran A, Khafagy A, Leong M, Shoham Z. Embryo catheter loading and embryo culture techniques: results of a worldwide Web-based survey. J Assist Reprod Genet. 2014 Aug;31(8):1029-36. doi: 10.1007/s10815-014-025 — View Citation

Dumoulin JC, Meijers CJ, Bras M, Coonen E, Geraedts JP, Evers JL. Effect of oxygen concentration on human in-vitro fertilization and embryo culture. Hum Reprod. 1999 Feb;14(2):465-9. doi: 10.1093/humrep/14.2.465. — View Citation

Gomes Sobrinho DB, Oliveira JB, Petersen CG, Mauri AL, Silva LF, Massaro FC, Baruffi RL, Cavagna M, Franco JG Jr. IVF/ICSI outcomes after culture of human embryos at low oxygen tension: a meta-analysis. Reprod Biol Endocrinol. 2011 Nov 1;9:143. doi: 10.11 — View Citation

Guerin P, El Mouatassim S, Menezo Y. Oxidative stress and protection against reactive oxygen species in the pre-implantation embryo and its surroundings. Hum Reprod Update. 2001 Mar-Apr;7(2):175-89. doi: 10.1093/humupd/7.2.175. — View Citation

Kaser DJ, Bogale B, Sarda V, Farland LV, Williams PL, Racowsky C. Randomized controlled trial of low (5%) versus ultralow (2%) oxygen for extended culture using bipronucleate and tripronucleate human preimplantation embryos. Fertil Steril. 2018 Jun;109(6) — View Citation

Kea B, Gebhardt J, Watt J, Westphal LM, Lathi RB, Milki AA, Behr B. Effect of reduced oxygen concentrations on the outcome of in vitro fertilization. Fertil Steril. 2007 Jan;87(1):213-6. doi: 10.1016/j.fertnstert.2006.05.066. Epub 2006 Nov 1. — View Citation

Kovacic B, Sajko MC, Vlaisavljevic V. A prospective, randomized trial on the effect of atmospheric versus reduced oxygen concentration on the outcome of intracytoplasmic sperm injection cycles. Fertil Steril. 2010 Jul;94(2):511-9. doi: 10.1016/j.fertnster — View Citation

Meintjes M, Chantilis SJ, Douglas JD, Rodriguez AJ, Guerami AR, Bookout DM, Barnett BD, Madden JD. A controlled randomized trial evaluating the effect of lowered incubator oxygen tension on live births in a predominantly blastocyst transfer program. Hum R — View Citation

Nastri CO, Nobrega BN, Teixeira DM, Amorim J, Diniz LMM, Barbosa MWP, Giorgi VSI, Pileggi VN, Martins WP. Low versus atmospheric oxygen tension for embryo culture in assisted reproduction: a systematic review and meta-analysis. Fertil Steril. 2016 Jul;106 — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number and grad of embryos which exposed to oxygen concentration 2% .	Evaluate embryo quality at day 5	1.3 year
Secondary	Clinical pregnancy rate for examined subject.	Compare the two arms in clinical pregnancy.	1.5 Year