Triple-arm pH Comparison

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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In Vitro Fertilisation Outcome

Intervention / Treatment
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* 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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women age of ≥ 18 to ≤ 40 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). Normal responder (≥ 10 antral follicle count (AFC) during basal ultrasound examination) PCOS Women who have ≥ 1 year of primary or secondary infertility Tubal factor (unilateral, bilateral obstruction or salpingectomy) Normal semen parameters Male factor: oligoasthenozoospermia or obstructive azoospermia Women who are undergoing their first IVF or ICSI cycle or second IVF Cycle with previous successful attempt Women who will undergo only fresh embryo transfer Women who have normal endometrial thickness (> 7 mm) and echo-pattern at the time of hCG trigger 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: Women who had unilateral oophorectomy Women who had uterine pathology or abnormality Women or their husbands who had abnormal karyotyping Women with history of recurrent abortions or repeated implantation failures Women who had uncontrolled diabetes Women with diagnosed or undiagnosed liver or renal disease Women who had a history of severe ovarian hyperstimulation Women who had history of malignancy or borderline pathology Women who will not meet the inclusion criteria Women who will refuse to participate in the study Women with endometriosis Patient undergoing PGS or PGD Severe male factor and non-obstructive azoospermia.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Transfer embryos from 7.20±0.02 pH<br>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<br>* 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.<br>|
| Experimental: Transfer embryos from 7.3±0.02 pH<br>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<br>* 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.<br>|
| Experimental: Transfer embryo from 7.4±0.02<br>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<br>* 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<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pH, IVF, live birth rate