Fresh Versus Freeze-only After CAPA IVM on PCOS Patients

Study Overview
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Brief Summary
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IVM (in vitro maturation) has been proved to be a more friendly treatment protocol for PCOS (polycystic ovary syndrome) patients compared with conventional controlled ovarian stimulation, with less complications (especially ovarian hyperstimulation syndrome), shorter treatment duration, lower cost, and acceptable pregnancy outcomes.

Detailed Description
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IVM (in vitro maturation) has been proved to be a more friendly treatment protocol for PCOS (polycystic ovary syndrome) patients compared with conventional controlled ovarian stimulation, with less complications (especially ovarian hyperstimulation syndrome), shorter treatment duration, lower cost, and acceptable pregnancy outcomes. CAPA (capacitation) IVM without hCG (human chorionic gonadotropin) priming, has routinely been used at My Duc hospital for nearly 3 years to replace hCG-IVM (with hCG priming) because of absolutely synchronized oocyte maturation stage and better embryo results and better pregnancy outcomes. However, with CAPA IVM, embryos are freezed-only and will be transferred in the next cycles. This process will increase the cost of freezing and thawing embryos, and increase the treatment duration, which complicates the IVM procedure and turns IVM into an unfriendly protocol to PCOS patients. Therefore, our group conducts this study to find out the effectiveness of fresh transfer protocol after CAPA IVM compared with freezing-only CAPA IVM protocol. The fresh transfer protocol for CAPA IVM is applied from previous hCG IVM protocol, with the use of hCG and exogenous estradiol and progesterone, but at different timings.

Official Title
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Outcomes of Fresh Transfer Versus Freeze-only After CAPA IVM on PCOS Patients

Conditions
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PCOS, IVM, Embryo Transfer

Intervention / Treatment
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* Procedure: CAPA-Fresh
* Procedure: CAPA-Freeze-only


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women with high AFC (≥24 Antral Follicles in Both Ovaries), including PCOS plus PCO or high AFC Having indications for ART Having ≤ 2 IVM/IVF attempts Permanent resident in Vietnam Agree to have fresh embryos transfer or freeze-only on day 3 Agree to have ≤ 2 embryos transferred Not participating in another IVF study at the same time Exclusion Criteria: Oocyte donation cycles Pre-implantation genetic diagnosis (PGD) cycles

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 37 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: CAPA-Fresh<br>Receiving FSH (Menopur, Ferring) for 2 days on day 2/3 of the menstrual cycle (spontaneous/ OCP administration) and an ultrasound scan will be performed subsequently. Oocytes retrieval will be performed 42 hours after the last injection. Receiving hCG 5000IU x 2 (10000IU) after Oocytes retrieval. Pre-maturation will last for 24-30 hours. ICSI will be used for insemination. Fresh embryos transfer will be performed on day 3 using HRT protocol with a maximum of 2 embryos transferred. | Procedure: CAPA-Fresh<br>* Receiving FSH (Menopur, Ferring) for 2 days on day 2/3 of the menstrual cycle (spontaneous/ OCP administration) and an ultrasound scan will be performed subsequently. Oocytes retrieval will be performed 42 hours after the last injection. Receiving hCG 5000IU x 2 (10000IU) after Oocytes retrieval. Pre-maturation will last for 24-30 hours. ICSI will be used for insemination. Fresh embryos transfer will be performed on day 3 using HRT protocol with a maximum of 2 embryos transferred.<br>|
| Active Comparator: CAPA-Freeze-only<br>Receiving FSH (Menopur, Ferring) for 2 days on day 2/3 of the menstrual cycle (spontaneous/ OCP administration) and an ultrasound scan will be performed subsequently. Oocytes retrieval will be performed 42 hours after the last injection. Pre-maturation will last for 24-30 hours. ICSI will be used for insemination. Freeze-only on day 3 and frozen embryo transfer will be performed on the subsequent cycle using HRT protocol with a maximum of 2 embryos transferred | Procedure: CAPA-Freeze-only<br>* Receiving FSH (Menopur, Ferring) for 2 days on day 2/3 of the menstrual cycle (spontaneous/ OCP administration) and an ultrasound scan will be performed subsequently. Oocytes retrieval will be performed 42 hours after the last injection. Pre-maturation will last for 24-30 hours. ICSI will be used for insemination. Freeze-only on day 3 and frozen embryo transfer will be performed on the subsequent cycle using HRT protocol with a maximum of 2 embryos transferred.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ongoing pregnancy resulting in live birth after the first embryo transfer of the started treatment cycle. | Live birth is defined as the birth of at least one newborn after 24 weeks' gestation that exhibits any sign of life (twin will be a single count). For the timing of this occur, ongoing pregnancy will be used, conditional on the fact that this ongoing pregnancy results in live birth. | At 24 weeks of gestation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Positive pregnancy test | Serum human chorionic gonadotropin level greater than 5 mIU/mL | at 2 weeks after the embryo placement after the completion of the first transfer | 
| Clinical pregnancy | at least one gestational sac on ultrasound at 7 weeks' gestation with the detection of heart beat activity | 5 weeks after embryo placement after the completion of the first transfer | 
| Implantation rate | as the number of gestational sacs per number of embryos transferred | 3 weeks after embryo transferred after the completion of the first transfer | 
| Ongoing pregnancy | Ongoing pregnancy is defined as pregnancy with detectable heart rate at 12 weeks' gestation or beyond, after the completion of the first transfer | At 12 weeks' gestation | 
| Number of embryos on day 3 | Number of embryos on day 3 | 5 days after oocytes pick-up | 
| Number of good quality embryo on day 3 | good quality embryos are defined followed Istanbul consensus | 5 days after oocytes pick-up | 
| Time from randomisation to ongoing pregnancy | Time from randomization to ongoing pregnancy after the completion | 12 weeks of gestation after the completion of the first transfer | 
| Time from randomisation to live birth | Time from randomization to live birth after the completion | At the time of delivery | 
| Ovarian hyperstimulation syndrome (OHSS) | Routine assessments for OHSS were performed on day 3 post oocyte retrieval in both groups. At other times, OHSS was evaluated if symptoms were reported by the patient. OHSS was classified using the flow diagram developed by Humaidan and colleagues for use in clinical trial settings | at 03 days after oocytes pick-up and 14 days after embryo transfer | 
| Ectopic pregnancy | a pregnancy in which implantation takes place outside the uterine cavity after the completion of the first transfer | at 12 weeks of gestation after the completion of the first transfer | 
| Miscarriage | pregnancy loss at < 24 weeks | at 24 weeks of gestation after the completion of the first transfer | 
| Hypertensive disorders of pregnancy | Pregnancy-induced hypertension, pre-eclampsia and eclampsia | at 20 weeks of gestation or beyond after the completion of the first transfer | 
| Gestational diabetes mellitus | using a 75g oral glucose tolerance test | at 24 weeks of gestation after the completion of the first transfer | 
| Preterm delivery | Multiple definitions, defined as delivery at <24, <28, <32, <37 completed weeks | at 24, 28, 32 weeks and 37 weeks of gestation after the completion of the first transfer | 
| Multiple pregnancy | Defined as presence of more than one sac at early pregnancy ultrasound (6-8 weeks gestation) | 5 weeks after embryo placement after the completion of the first transfer | 
| Birth weight | Weight of singletons and twins | at the time of delivery | 
| Congenital anomaly | Any congenital anomaly will be included | At birth after the completion of the first transfer | 
| Cost-effectiveness | Including direct and indirect costs; costs related to complications treatment. Cost data will be collected for a supplementary analysis and will be reported in a separated paper. | Two year after randomization |