Non-FSH vs FSH-priming in Cycles With CAPA-IVM Treatment

NCT ID: NCT05600972

Last Updated: 2024-12-27

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

120 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-01-02

Study Completion Date

2024-04-25

Brief Summary

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In vitro oocyte maturation (IVM) is an assisted reproductive technology requiring minimal or no ovarian stimulation. In this technique, the immature oocytes were retrieved from follicles and subsequently cultured matured, meaning that GV oocytes reached MII in vitro (ASRM, 2021).

Currently, there is no consensus on the unique IVM protocol. However, recommended protocols that are being utilized include IVM with and without hCG (Standard IVM) and CAPA-IVM.

As mentioned previously, FSH priming before oocyte retrieval for IVM remains controversial. However, FSH is known as a hormone for the maturation of the follicles. Therefore, during oocyte maturation (IVM) cycles, FSH is used to "prime" follicular development. Generally, many studies showed a trend of a higher number of MII oocytes obtained after IVM after using FSH priming.

In animal models, Younis et al. (1994) observed a significant increase in the number of mature oocytes when performing IVM in cynomolgus monkeys (Macaca fascicularis) with a dose of 1000 IU of PMSG (pregnant mare's serum gonadotropin) in the follicular phase (Younis et al., 1994). Similarly, Wynn et al. (1998) conducted a study on mice. The results from this study revealed that a higher number of MII oocytes was observed. Still, the blastulation rate and the number of blastomeres were significantly lower than that without FSH priming. On the other hand, FSH activates meiosis resumption (Wynn et al., 1998).

In addition, an RCT of 28 patients comparing three days of 150 IU of FSH before the IVM aspiration group with the control group also showed an improvement in implantation rates in IVM cycles with FSH priming (Mikkelsen et al., 2001). The studies mentioned above both used the non-hCG IVM protocol. Other studies by Shalom-Paz et al. (2011) and Choavaratana et al. (2015) showed superiority in the number of MII oocytes.

There has been no data on the impact of not using FSH priming in CAPA-IVM cycles. Therefore, this RCT will investigate the efficacy of CAPA-IVM with and without FSH priming.

Detailed Description

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3.1. Screening for eligibility and randomization

* This trial will be conducted at My Duc Hospital, Ho Chi Minh City, Viet Nam.
* Women who are potentially eligible will be provided information about the trial at the time of IVM treatment indication.
* Screening for eligibility will be performed on the day of the first visit when the IVM treatment is indicated.
* Patients will be provided information related to the study together with the informed consent documents. Signed informed consent forms will be obtained by the investigators from all women before the enrolment.
* All patients selected for this study will undergo a 7-day COCPs administration to induce menstruation before entering both arms.
* Women will be randomized (1:1) to either non-FSH or FSH priming:

3.2 Oocytes retrieval The oocyte retrieval will be performed four days after the randomization, accordingly to the current routine procedures.

* An ultrasound scan will be performed to exclude the development of any dominant follicle.
* Patients randomized into the FSH priming arm will receive two days of FSH injections at 150 IU/day.
* Oocyte retrieval will be scheduled 42 hours after the last FSH injection.
* In the non-FSH arm, the COC will be retrieved on the same retrieval day as the FSH-treated arm.
* All the punctured follicular cohorts will be monitored carefully by ultrasound on the day before and on OPU day.

3.3 CAPA and Maturation culture: CAPA and Maturation culture will be performed routinely following current laboratory protocols.

* ICSI will be used for the fertilization of mature oocytes.
* The freeze-only will be performed, and all good embryos will be frozen on day 5 for subsequent embryo transfer.

3.4 Frozen embryo transfer After oocyte retrieval, a blister of oral contraceptive pills will be indicated to induce the bleeding.

Endometrial preparation with hormonal replacement therapy will be performed. In the following cycle, the endometrium will be prepared using oral estradiol valerate (Valiera®; Laboratories Recalcine) 8 mg/day starting from the second or third day of the menstrual cycle. The endometrial thickness will be monitored from day six onwards, and vaginal progesterone (Cyclogest®; Actavis) 800 mg/day will be started when endometrial thickness reached 7 mm or more. Elective single embryo transfer with a blastocyst will be performed. Embryos will be thawed on the day of embryo transfer, five days after the start of progesterone. Two hours after thawing, surviving embryos will be transferred into the uterus under ultrasound guidance. Embryos will be transferred into the uterine cavity.

3.5 Pregnancy test and ultrasound to confirm fetal viability: A pregnancy test will be performed by measuring the blood beta-hCG level two weeks after embryo transfer. If the pregnancy test is positive (≥25mIU/mL), the patient is indicated to use exogenous estrogen (transdermal or oral) and progesterone until at least 12 weeks of gestation. A pregnancy ultrasound will be performed three weeks after the positive pregnancy test equal to 7 weeks of gestational age.

3.6 Obstetric and neonatal outcomes: All data relating to the delivery process and neonatal care will be recorded by the data management system of IVFMD.

Conditions

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in Vitro Maturation FSH Priming

Keywords

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in vitro maturation, FSH priming

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Investigators
Embryologists are blinded to individual clinical treatment allocation

Study Groups

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non-FSH priming

Routine CAPA-IVM treatment will be performed. The oocyte retrieval will be performed 2 days after the randomization accordingly to the current routine procedures. An ultrasound scan will be performed to exclude the development of any dominant follicle.

Group Type NO_INTERVENTION

No interventions assigned to this group

FSH priming

Routine CAPA-IVM treatment will be performed. Patients who are randomized into the FSH priming arm will receive two days of FSH injections of 150 IU/day. Oocyte retrieval will be scheduled at 42 hours after the last FSH injection.

Group Type ACTIVE_COMPARATOR

FSH priming

Intervention Type PROCEDURE

Patients who are randomized into the FSH priming arm will receive two days of FSH injections of 150 IU/day. Oocyte retrieval will be scheduled at 42 hours after the last FSH injection.

Interventions

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FSH priming

Patients who are randomized into the FSH priming arm will receive two days of FSH injections of 150 IU/day. Oocyte retrieval will be scheduled at 42 hours after the last FSH injection.

Intervention Type PROCEDURE

Eligibility Criteria

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Inclusion Criteria

* Aging from 18 to 37
* Diagnosed with PCOS followed by Rotterdam criteria
* Having an indication for CAPA-IVM treatment
* Agree to have all embryos frozen on day 5/6.
* Agree to have one blastocyst (if of good quality defined as 3BB or above) or up to two blastocysts (if no good quality are available) transferred in a subsequent frozen transfer
* Having ≤ 2 IVM/IVF attempts

Exclusion Criteria

* A previous ovarian stimulation (for OI or IVF) within the previous three months
* Cycles with oocytes donation
* Uterine or ovarian abnormalities
* Previous evidence of a very low oocyte maturation without suspicion of FSH /LH receptor defect
* Cycles with sperms retrieved after PESA/TESE/microTESE
Minimum Eligible Age

18 Years

Maximum Eligible Age

37 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Mỹ Đức Hospital

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Lan N Vuong, M.D., Ph.D.

Role: PRINCIPAL_INVESTIGATOR

IVFMD and HOPE Research Center, My Duc Hospital

Locations

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IVFMD - My Duc Hospital

Ho Chi Minh City, , Vietnam

Site Status

Countries

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Vietnam

References

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Vuong LN, Ho VNA, Le AH, Nguyen NT, Pham TD, Nguyen MHN, Le HL, Le TK, Ha AN, Le XTH, Pham HH, Tran CT, Huynh BG, Smitz JEJ, Gilchrist RB, Ho TM. Hormone-free vs. follicle-stimulating hormone-primed infertility treatment of women with polycystic ovary syndrome using biphasic in vitro maturation: a randomized controlled trial. Fertil Steril. 2025 Feb;123(2):253-261. doi: 10.1016/j.fertnstert.2024.09.010. Epub 2024 Sep 12.

Reference Type DERIVED
PMID: 39260537 (View on PubMed)

Other Identifiers

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13/22/DD-BVMD

Identifier Type: -

Identifier Source: org_study_id