Clinical trial NCT04424784: Influence of Manipulation of Oocytes and Embryos in Low Oxygen Tension on Assisted Reproduction Technology Outcome
Official title: Influence of Manipulation of Oocytes and Embryos in Low Oxygen Tension on Assisted Reproduction Technology Outcome
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Embryo Hypoxia
Lead sponsor: The University of Hong Kong-Shenzhen Hospital
Sponsor class: OTHER
First posted: 2020-06-11
Enrollment: 1160
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: Nowadays, most assisted reproduction laboratories attempt to maintain as much as possible ex vivo culture conditions comparable to those in vivo. Various culturing condition such as temperature and pH parameters have been adjusted according to in vivo values in order to improve in-vitro fertilization (IVF) outcomes. Embryos of most mammals, including that of humans, are not exposed to oxygen concentration higher than 8%. Thus, embryos and gametes should be kept in a low oxygen environment during manipulation in assisted reproduction treatment.

Culturing embryos in low oxygen concentrations is now a general practice in IVF laboratories. However, there are still laboratory procedures when the oocytes/embryos are exposed to atmospheric oxygen. In most laboratories, oocytes retrieval is performed under atmospheric oxygen concentration. Oocyte is very sensitive to environmental changes, for instance, transient cooling to room temperature can cause irreversible disruption of the meiotic spindle in human oocytes and oocyte in vitro maturation can lead to the decline of energy metabolism in human oocytes. Whether oocyte exposed to atmospheric oxygen during oocyte retrieval has detrimental effect on embryo development and IVF outcomes is unknown.

Previous studies showed that low oxygen tension during embryo culture improved implantation rate and clinical outcomes, but embryo quality was not affected. In other studies, embryo quality was improved but overall pregnancy was not affected. The reason for the discrepancies could be because the oxygen tension during oocyte/embryo manipulation was not under well control. For instance, oocyte retrieval, fertilization check and embryo grading were performed under atmospheric oxygen. It is difficult to predict how these factors negatively impact the IVF outcomes.

In this project, the investigators hypothesize that lower oxygen tension during oocyte/embryo manipulation improves IVF outcomes.

Detailed description: In the experimental group, oocyte pickup will be performed in a lower oxygen tension environment (5% oxygen, 89% nitrogen, 6% carbon dioxide); oocyte pickup will be performed in a special workstation with reduced oxygen tension environment while fertilization check and embryo grading will be performed in conventional and time lapse embryo culture system. The time lapse culture system can provide a constant lower oxygen tension culture environment to the embryos. In the control group, oocyte pickup, fertilization check and embryo grading will be performed in atmospheric oxygen environment. Under this arrangement, the difference between the 2 groups is the oxygen tension during oocyte/embryo manipulation. The investigators believe that a solid conclusion can be drawn about whether lower oxygen tension environment can benefit IVF outcomes.

Eligibility criteria: Inclusion Criteria:

* all the couples undergoing conventional IVF cycle in the reproductive medicine center of the University of Hong Kong-Shenzhen Hospital

Exclusion Criteria:

* Intracytoplasmic sperm injection (ICSI) cycle
* Preimplantation genetic testing (PGT) cycle
* cycle with fertilization failure ≥3
* cycle using sperm from percutaneous epididymal sperm aspiration (PESA)/testicular sperm extraction (TESE) or cryopreserved sperm
* cycle using cryopreserved oocyte
* cycle with no oocyte retrieved

Primary outcomes:
measure: live birth rate
timeFrame: 4 years
Secondary outcomes:
measure: clinical pregnancy rate
timeFrame: 3 years
measure: ongoing pregnancy rate
timeFrame: 3 years
measure: fertilization rate
timeFrame: 3 years
measure: cleavage rate
timeFrame: 3 years
Other outcomes:
Locations:
city: Shenzhen
country: China
facility: Reproductive medicine center
Study officials:
affiliation: The University of Hong Kong-Shenzhen Hospital
name: Shubiu Yeung, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Fischer B, Bavister BD. Oxygen tension in the oviduct and uterus of rhesus monkeys, hamsters and rabbits. J Reprod Fertil. 1993 Nov;99(2):673-9. doi: 10.1530/jrf.0.0990673.
citation: Kovacic B, Vlaisavljevic V. Influence of atmospheric versus reduced oxygen concentration on development of human blastocysts in vitro: a prospective study on sibling oocytes. Reprod Biomed Online. 2008 Aug;17(2):229-36. doi: 10.1016/s1472-6483(10)60199-x.
citation: Waldenstrom U, Engstrom AB, Hellberg D, Nilsson S. Low-oxygen compared with high-oxygen atmosphere in blastocyst culture, a prospective randomized study. Fertil Steril. 2009 Jun;91(6):2461-5. doi: 10.1016/j.fertnstert.2008.03.051. Epub 2008 Jun 12.