Clinical trial NCT05600972: Non-FSH vs FSH-priming in Cycles With CAPA-IVM Treatment
Official title: The Efficiency of Non-FSH Versus FSH-priming in CAPA-IVM Cycles: a Randomized Clinical Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: in Vitro Maturation
FSH Priming
Keywords: in vitro maturation, FSH priming
Lead sponsor: Mỹ Đức Hospital
Sponsor class: OTHER
First posted: 2022-11-01
Enrollment: 120
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 37
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of matured oocytes after CAPA-IVM cultured
timeFrame: 2 day after oocyte retrieval
Secondary outcomes:
measure: Positive pregnancy test rate
timeFrame: 2 weeks after embryo transfer
measure: Implantation rate
timeFrame: 3 weeks after embryo transfer
measure: Ectopic pregnancy rate
timeFrame: 4 weeks after embryo transfer
measure: Clinical pregnancy rate
timeFrame: 5 weeks after embryo transfer
measure: Ongoing pregnancy rate
timeFrame: 10 weeks after embryo transfer
measure: Miscarriage rate
timeFrame: 2-10 weeks after embryo transfer
measure: Live birth rate
timeFrame: After delivery at 12 months after randomization
measure: Multiple pregnancy rate
timeFrame: 5 weeks after embryo transfer
measure: Preterm delivery rate
timeFrame: At delivery at 12 months after randomization
measure: Birth weight
timeFrame: At delivery at 12 months after randomization
measure: Gestational diabetes mellitus
timeFrame: At 24 weeks of gestation or beyond at 12 months after randomization
measure: Hypertensive disorders of pregnancy
timeFrame: At 20 weeks of gestation or beyond at 12 months after randomization
measure: Antepartum hemorrhage
timeFrame: After delivery at 12 months after randomization
measure: Large for gestational age
timeFrame: After delivery at 12 months after randomization
measure: Small for gestational age
timeFrame: After delivery at 12 months after randomization
measure: Congenital anomaly
timeFrame: After delivery at 12 months after randomization
measure: Perinatal mortality
timeFrame: After delivery at 12 months after randomization
measure: Admission to NICU
timeFrame: After delivery at 12 months after randomization
Other outcomes:
Locations:
city: Ho Chi Minh City
country: Vietnam
facility: IVFMD - My Duc Hospital
Study officials:
affiliation: IVFMD and HOPE Research Center, My Duc Hospital
name: Lan N Vuong, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
References: