Triple-arm pH Comparison

Not Applicable

Completed

• Conditions: In Vitro Fertilisation Outcome
• Interventions: Other: Transfer embryo from pH 7.3±0.02 either Day 3 or day 5/6; Other: Transfer embryo from pH 7.20±0.02 on 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

• Registration Number: NCT02896777
• Lead Sponsor: Ibn Sina Hospital

Brief Summary

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.

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 Timeline

• Study First Submitted: 2016-08-31
• Study First Submitted QC: 2016-09-09
• Study First Posted: 2016-09-12
• Study Start: 2020-06-13
• Primary Completion: 2023-04-27
• Status Verified: 2023-08
• Study Completion: 2023-08-11
• Last Update Submitted: 2023-08-16
• Last Update Posted: 2023-08-21

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 2273

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Transfer embryos from 7.3±0.02 pH	Transfer embryo from pH 7.3±0.02 either Day 3 or day 5/6	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.
Transfer embryos from 7.20±0.02 pH	Transfer embryo from pH 7.20±0.02 on either Day 3 or day 5/6	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.
Transfer embryo from 7.4±0.02	Transfer embryo from pH of 7.4±0.02 on either Day 3 or day 5/6	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.

Primary Outcome Measures

Name	Time	Method
live-birth rate	> 20 weeks of gestation	delivery of one or more viable infants \> 20 weeks of gestation

Secondary Outcome Measures

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

Trial Locations

Locations (6)

Qena Fertility Center; 🇪🇬 Qena, Egypt

Amshaj; 🇪🇬 Sohag, Egypt

IbnSina IVF Center; 🇪🇬 Sohag, Egypt

Egyptian IVF-ET Center; 🇪🇬 Cairo, Egypt

Royal Centre; 🇪🇬 Mansoura, Egypt

Banon Assiut; 🇪🇬 Assiut, Egypt