Fresh Versus Freeze-only After CAPA IVM on PCOS Patients

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

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.

Study Overview

• Status: Completed
• Conditions: PCOS; Embryo Transfer; IVM
• Intervention / Treatment: Procedure: CAPA-Fresh; Procedure: CAPA-Freeze-only

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Vietnam
  • Tan Binh
    • Ho Chi Minh City, Tan Binh, Vietnam
      • Mỹ Đức Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 37 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: CAPA-Fresh; 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; 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.
ACTIVE_COMPARATOR: CAPA-Freeze-only; 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; 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.

What is the study measuring?

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
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
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

Collaborators and Investigators

• Sponsor: Mỹ Đức Hospital

Publications and helpful links

General Publications

• Vuong LN, Nguyen LK, Le AH, Pham HH, Ho VN, Le HL, Pham TD, Dang VQ, Phung TH, Smitz J, Ho TM. Fresh embryo transfer versus freeze-only after in vitro maturation with a pre-maturation step in women with high antral follicle count: a randomized controlled pilot study. J Assist Reprod Genet. 2021 Jun;38(6):1293-1302. doi: 10.1007/s10815-021-02180-7. Epub 2021 Apr 6.

Study record dates

Study Major Dates

• Study Start (ACTUAL): March 6, 2020
• Primary Completion (ACTUAL): August 18, 2020
• Study Completion (ACTUAL): December 15, 2020

Study Registration Dates

• First Submitted: March 2, 2020
• First Submitted That Met QC Criteria: March 3, 2020
• First Posted (ACTUAL): March 5, 2020

Study Record Updates

• Last Update Posted (ACTUAL): February 24, 2021
• Last Update Submitted That Met QC Criteria: February 22, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Other Study ID Numbers: CS/BVMĐPN/20/01

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