Triple-arm pH Comparison (Tri-pH)

Triple-arm Trial of pH (Tri-pH) Effect on Live Birth After ICSI

The culturing human embryo in vitro is a process of myriad contributing elements. From these factors is the pH of embryo culture media, which is crucial for embryo development. The investigators plan to examine three different pH values of the culture media on the live birth rate of in vitro cultured human embryos.

Study Overview

• Status: Completed
• Conditions: In Vitro Fertilisation Outcome
• Intervention / Treatment: Other: Transfer embryo from pH 7.20±0.02 on either Day 3 or day 5/6; Other: Transfer embryo from pH 7.3±0.02 either Day 3 or day 5/6; Other: Transfer embryo from pH of 7.4±0.02 on either Day 3 or day 5/6

Detailed Description

In vitro fertilisation laboratory is the black box in which early human embryo development of infertile couple occurs. This laboratory holds many variables such as incubator type, air quality, brands of culture media, culture temperature and the pH of culture medium. Despite the importance of the culture medium pH, there is no single RCT has examined its effect on live birth rate post in vitro fertilisation. The investigators of this study believe that leaving this crucial element to the wishes of large companies and media designers is unwise. This RCT aims to provide a conclusive answer on pH effect on live birth rate of in vitro cultured human embryos.

• Study Type: Interventional
• Enrollment (Actual): 2273
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Egypt
  • Assiut, Egypt
    • Banon Assiut
  • Cairo, Egypt
    • Egyptian IVF-ET Center
  • Mansoura, Egypt, 123456
    • Royal Centre
  • Qena, Egypt, 123456
    • Qena Fertility Center
  • Sohag, Egypt
    • IbnSina IVF Center
  • Sohag, Egypt, 12345
    • Amshaj

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Women age of ≥ 18 to ≤ 40
2. BMI of ≤ 35 (After approval of the DMC on 19 Feb 2021 and the IRB thereafter, BMI is changed from ≤31 to ≤35 based on clinician request. DMC).
3. Normal responder (≥ 10 antral follicle count (AFC) during basal ultrasound examination)
4. PCOS
5. Women who have ≥ 1 year of primary or secondary infertility
6. Tubal factor (unilateral, bilateral obstruction or salpingectomy)
7. Normal semen parameters
8. Male factor: oligoasthenozoospermia or obstructive azoospermia
9. Women who are undergoing their first IVF or ICSI cycle or second IVF Cycle with previous successful attempt
10. Women who will undergo only fresh embryo transfer
11. Women who have normal endometrial thickness (> 7 mm) and echo-pattern at the time of hCG trigger
12. Women who have normal transvaginal ultrasound during the follicular phase (defined as no intra cavity pathology; e.g. submucousal myomas, polyps or septa)

Exclusion Criteria:

1. Women who had unilateral oophorectomy
2. Women who had uterine pathology or abnormality
3. Women or their husbands who had abnormal karyotyping
4. Women with history of recurrent abortions or repeated implantation failures
5. Women who had uncontrolled diabetes
6. Women with diagnosed or undiagnosed liver or renal disease
7. Women who had a history of severe ovarian hyperstimulation
8. Women who had history of malignancy or borderline pathology
9. Women who will not meet the inclusion criteria
10. Women who will refuse to participate in the study
11. Women with endometriosis
12. Patient undergoing PGS or PGD
13. Severe male factor and non-obstructive azoospermia.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Transfer embryos from 7.20±0.02 pH; In this arm, the intervention is to culture the inseminated oocytes in vitro in a pH of 7.2±0.02 from day 0 to 5/6 post IVF/ICSI. Then according to the result of the randomization, women will receive their embryos that will be cultured in this pH on either Day 3 or Day 5/6 post IVF/ICSI.	Other: Transfer embryo from pH 7.20±0.02 on either Day 3 or day 5/6; Post IVF/ICSI and according to the result of the randomization process, women will receive embryo from their oocytes that will be cultured in pH of 7.20±0.02.
Experimental: Transfer embryos from 7.3±0.02 pH; In this arm, the intervention is to culture the inseminated oocytes in vitro in a pH of 7.3±0.02 from day 0 to 5/6 post IVF/ICSI. Then according to the result of the randomization, women will receive their embryos that will be cultured in this pH on either Day 3 or Day 5/6 post IVF/ICSI.	Other: Transfer embryo from pH 7.3±0.02 either Day 3 or day 5/6; Post IVF/ICSI and according to the result of the randomization process, women will receive embryo from their oocytes that will be cultured in pH of 7.3±0.02.
Experimental: Transfer embryo from 7.4±0.02; In this arm, the intervention is to culture the inseminated oocytes in vitro in a pH of 7.4±0.02 from day 0 to 5/6 post IVF/ICSI. Then according to the result of the randomization, women will receive their embryos that will be cultured in this pH on either Day 3 or Day 5/6 post IVF/ICSI.	Other: Transfer embryo from pH of 7.4±0.02 on either Day 3 or day 5/6; Post IVF/ICSI and according to the result of the randomization process, women will receive embryo from their oocytes that will be cultured in pH of 7.4±0.02 from day 0 to 5/6

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
live-birth rate	delivery of one or more viable infants > 20 weeks of gestation	> 20 weeks of gestation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Biochemical pregnancy rate	registered positive hCG ≥14 days after egg collection	within 7 weeks of gestation
Clinical pregnancy rate	presence of a foetal sac with a foetal heart beat on ultrasound > 7 weeks of presence of a foetal sac with a foetal heart beat on ultrasound > 7 weeks of gestation	≥ 7 weeks of gestation
Ongoing pregnancy rate	Continued pregnancy after 20 weeks of gestation	within 24 weeks of pregnancy
Miscarriage rate	Loss of pregnancy before week 20 of gestation	within 42 weeks of pregnancy
Term Live birth rate	Delivery of one or more viable infants ≥ 37 weeks of gestation	≥ 37 weeks of gestation
Live-birth-implantation rate	Number of viable neonates per number of embryos transferred	within 42 weeks of gestation
Cumulative live birth after one fresh and one frozen transfer	Registered live birth from one fresh and one frozen cycles	within one year from randomization
Preterm Birth rate	Delivery of one or more viable infants <37 weeks of gestation	<37 weeks of gestation
Very preterm birth rate	Delivery of one or more viable infants <32 weeks of gestation	<32 weeks of gestation
Still birth	delivery of nonviable babies > 20 weeks of gestation	42 weeks after ICSI
Low birth weight babies	Viable neonate < 2500 gm within 24 hours of delivery	24 hours after delivery
Congenital malformation	delivery of congenitally malformed babies	within 42 weeks of gestation
Fertilisation rate	Presence of 2 pronuclei17±1 hr post insemination/ICSI	Within 18 hours of inseminating the oocyte
Cleavage rate	registered divided embryo per fertilised oocyte	Within 72 hours of inseminating the oocytes
High quality embryo on day 3	embryo of 7 or more appropriate-size blastomeres with < 10 fragmentation by volume per Istanbul Consensus	Within 72 hours of inseminating the oocytes
Blastocyst formation rate on day 5/6	Formed blastocyst of any grade on day 5 or 6 per fertilized oocyte	Within 5-7 days of inseminating the oocytes
High-quality blastocyst rate on day 5	Blastocyst of ≥ 3.1.1.grading per Istanbul Consensus on day 5	5 Days of inseminating the oocytes
Cryopreservation rate on day 5/6	Number of cryopreserved blastocyst on day 5 and 6 per fertilized oocyte	5-7 Days of inseminating the oocytes
Embryo utilization rate	Embryo Utilization rate (number of cryopreserved embryos added to the transferred embryos per fertilized oocytes	5-7 days post ICSI
Top-quality embryo utilization rate	number of cryopreserved embryos added to the transferred embryos per fertilized oocytes	5-7 days post ICSI

Collaborators and Investigators

• Sponsor: Ibn Sina Hospital
• Collaborators: Banon IVF Center Assiut, Egypt; Egyptian IVF Center
• Investigators: Principal Investigator: Mohamed Fawzy, Ibnsina Hospital

Publications and helpful links

General Publications

• Fawzy M, Emad M, Wilkinson J, Mansour R, Mahran A, Fetih A, Abdelrahman M, AbdelGhafar H. Triple-arm trial of pH (Tri-pH) effect on live birth after ICSI in Egyptian IVF facilities: protocol of a randomised controlled trial. BMJ Open. 2020 Feb 4;10(2):e034194. doi: 10.1136/bmjopen-2019-034194.

Study record dates

Study Major Dates

• Study Start (Actual): June 13, 2020
• Primary Completion (Actual): April 27, 2023
• Study Completion (Actual): August 11, 2023

Study Registration Dates

• First Submitted: August 31, 2016
• First Submitted That Met QC Criteria: September 9, 2016
• First Posted (Estimated): September 12, 2016

Study Record Updates

• Last Update Posted (Actual): August 21, 2023
• Last Update Submitted That Met QC Criteria: August 16, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: IVF; pH; live birth rate
• Other Study ID Numbers: pH Study

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No